SCFAtPP2-B11 modulates ABA signaling by facilitating SnRK2.3 degradation in Arabidopsis thaliana

PubMed Central

Ren, Ziyin; Zhi, Liya; Yao, Bin; Su, Chao; Liu, Liu; Li, Xia

2017-01-01

The phytohormone abscisic acid (ABA) is an essential part of the plant response to abiotic stressors such as drought. Upon the perception of ABA, pyrabactin resistance (PYR)/PYR1-like (PYL)/regulatory components of ABA receptor (RCAR) proteins interact with co-receptor protein phosphatase type 2Cs to permit activation Snf1-related protein kinase2 (SnRK2) kinases, which switch on ABA signaling by phosphorylating various target proteins. Thus, SnRK2 kinases are central regulators of ABA signaling. However, the mechanisms that regulate SnRK2 degradation remain elusive. Here, we show that SnRK2.3 is degradated by 26S proteasome system and ABA promotes its degradation. We found that SnRK2.3 interacts with AtPP2-B11 directly. AtPP2-B11 is an F-box protein that is part of a SKP1/Cullin/F-box E3 ubiquitin ligase complex that negatively regulates plant responses to ABA by specifically promoting the degradation of SnRK2.3. AtPP2-B11 was induced by ABA, and the knockdown of AtPP2-B11 expression markedly increased the ABA sensitivity of plants during seed germination and postgerminative development. Overexpression of AtPP2-B11 does not affect ABA sensitivity, but inhibits the ABA hypersensitive phenotypes of SnRK2.3 overexpression lines. These results reveal a novel mechanism through which AtPP2-B11 specifically degrades SnRK2.3 to attenuate ABA signaling and the abiotic stress response in Arabidopsis. PMID:28787436

PP2B/calcineurin-mediated desensitization of TRPV1 does not require AKAP150

PubMed Central

Por, Elaine D.; Samelson, Bret K.; Belugin, Sergei; Akopian, Armen N.; Scott, John D.; Jeske, Nathaniel A.

2011-01-01

Activation of protein kinases and phosphatases at the plasma membrane often initiates agonist-dependent signalling events. In sensory neurons, AKAP150 (A-kinase-anchoring protein 150) orientates PKA (protein kinase A), PKC (protein kinase C) and the Ca2+/calmodulin-dependent PP2B (protein phosphatase 2B, also known as calcineurin) towards membrane-associated substrates. Recent evidence indicates that AKAP150-anchored PKA and PKC phosphorylate and sensitize the TRPV1 (transient receptor potential subfamily V type 1 channel, also known as the capsaicin receptor). In the present study, we explore the hypothesis that an AKAP150-associated pool of PP2B catalyses the dephosphorylation and desensitization of TRPV1. Biochemical, electrophysiological and cell-based experiments indicate that PP2B associates with AKAP150 and TRPV1 in cultured TG (trigeminal ganglia) neurons. Gene silencing of AKAP150 reduces basal phosphorylation of TRPV1. However, functional studies in neurons isolated from AKAP150−/− mice indicate that the anchoring protein is not required for pharmacological desensitization of TRPV1. Behavioural analysis of AKAP150−/− mice further support this notion, demonstrating that agonist-stimulated desensitization of TRPV1 is sensitive to PP2B inhibition and does not rely on AKAP150. These findings allow us to conclude that pharmacological desensitization of TRPV1 by PP2B may involve additional regulatory components. PMID:20883208

PP2B/calcineurin-mediated desensitization of TRPV1 does not require AKAP150.

PubMed

Por, Elaine D; Samelson, Bret K; Belugin, Sergei; Akopian, Armen N; Scott, John D; Jeske, Nathaniel A

2010-12-15

Activation of protein kinases and phosphatases at the plasma membrane often initiates agonist-dependent signalling events. In sensory neurons, AKAP150 (A-kinase-anchoring protein 150) orientates PKA (protein kinase A), PKC (protein kinase C) and the Ca2+/calmodulin-dependent PP2B (protein phosphatase 2B, also known as calcineurin) towards membrane-associated substrates. Recent evidence indicates that AKAP150-anchored PKA and PKC phosphorylate and sensitize the TRPV1 (transient receptor potential subfamily V type 1 channel, also known as the capsaicin receptor). In the present study, we explore the hypothesis that an AKAP150-associated pool of PP2B catalyses the dephosphorylation and desensitization of TRPV1. Biochemical, electrophysiological and cell-based experiments indicate that PP2B associates with AKAP150 and TRPV1 in cultured TG (trigeminal ganglia) neurons. Gene silencing of AKAP150 reduces basal phosphorylation of TRPV1. However, functional studies in neurons isolated from AKAP150-/- mice indicate that the anchoring protein is not required for pharmacological desensitization of TRPV1. Behavioural analysis of AKAP150-/- mice further support this notion, demonstrating that agonist-stimulated desensitization of TRPV1 is sensitive to PP2B inhibition and does not rely on AKAP150. These findings allow us to conclude that pharmacological desensitization of TRPV1 by PP2B may involve additional regulatory components.

AIP1 recruits phosphatase PP2A to ASK1 in tumor necrosis factor-induced ASK1-JNK activation.

PubMed

Min, Wang; Lin, Yan; Tang, Shibo; Yu, Luyang; Zhang, Haifeng; Wan, Ting; Luhn, Tricia; Fu, Haian; Chen, Hong

2008-04-11

Previously we have shown that AIP1 (apoptosis signal-regulating kinase [ASK]1-interacting protein 1), a novel member of the Ras-GAP protein family, facilitates dephosphorylation of ASK1 at pSer967 and subsequently 14-3-3 release from ASK1, leading to enhanced ASK1-JNK signaling. However, the phosphatase(s) responsible for ASK1 dephosphorylation at pSer967 has not been identified. In the present study, we identified protein phosphatase (PP)2A as a potential phosphatase in vascular endothelial cells (ECs). Tumor necrosis factor (TNF)-induced dephosphorylation of ASK1 pSer967 in ECs was blocked by PP2A inhibitor okadaic acid. Overexpression of PP2A catalytic subunit induced dephosphorylation of ASK1 pSer967 and activation of c-Jun N-terminal kinase (JNK). In contrast, a catalytic inactive form of PP2A or PP2A small interfering RNA blunted TNF-induced dephosphorylation of ASK1 pSer967 and activation of JNK without effects on NF-kappaB activation. Whereas AIP1, via its C2 domain, binds to ASK1, PP2A binds to the GAP domain of AIP1. Endogenous AIP1-PP2A complex can be detected in the resting state, and TNF induces a complex formation of AIP1-PP2A with ASK1. Furthermore, TNF-induced association of PP2A with ASK1 was diminished in AIP1-knockdown ECs, suggesting a critical role of AIP1 in recruiting PP2A to ASK1. TNF-signaling molecules TRAF2 and RIP1, known to be in complex with AIP1 and activate AIP1 by phosphorylating AIP1 at Ser604, are critical for TNF-induced ASK1 dephosphorylation. Finally, PP2A and AIP1 cooperatively induce activation of ASK1-JNK signaling and EC apoptosis, as demonstrated by both overexpression and small interfering RNA knockdown approaches. Taken together, our data support a critical role of PP2A-AIP1 complex in TNF-induced activation of ASK1-JNK apoptotic signaling.

[Contents of water-soluble vitamins in canned fish and seafood].

PubMed

Shmakova, S I; Shvidskaia, Z P; Dolbnina, L V

2000-01-01

Data of contents of vitamins (B1 and B2, C, PP) in production from gidrobionts is given. Is established, that the process of sterilization of canned food from gidrobionts in to container provides significant (almost twofold) decrease (reduction) of vitamins B1 [symbol: see text] B2, smaller losses of vitamin C (less than 30%) and proves to be true sufficient stability (almost on 85-90%) to action of high temperatures (120 degrees C) of vitamin PP. The canned food from sea gidrobionts represent the certain interest basically as a source of vitamin PP, and canned food "Herring smoked in oil"--vitamin B2. The canned food "Skobljanka from cucumber and fish" can be considered as a source of vitamins B2, C, PP.

Suppressor mutations identify amino acids in PAA-1/PR65 that facilitate regulatory RSA-1/B″ subunit targeting of PP2A to centrosomes in C. elegans.

PubMed

Lange, Karen I; Heinrichs, Jeffrey; Cheung, Karen; Srayko, Martin

2013-01-15

Protein phosphorylation and dephosphorylation is a key mechanism for the spatial and temporal regulation of many essential developmental processes and is especially prominent during mitosis. The multi-subunit protein phosphatase 2A (PP2A) enzyme plays an important, yet poorly characterized role in dephosphorylating proteins during mitosis. PP2As are heterotrimeric complexes comprising a catalytic, structural, and regulatory subunit. Regulatory subunits are mutually exclusive and determine subcellular localization and substrate specificity of PP2A. At least 3 different classes of regulatory subunits exist (termed B, B', B″) but there is no obvious similarity in primary sequence between these classes. Therefore, it is not known how these diverse regulatory subunits interact with the same holoenzyme to facilitate specific PP2A functions in vivo. The B″ family of regulatory subunits is the least understood because these proteins lack conserved structural domains. RSA-1 (regulator of spindle assembly) is a regulatory B″ subunit required for mitotic spindle assembly in Caenorhabditis elegans. In order to address how B″ subunits interact with the PP2A core enzyme, we focused on a conditional allele, rsa-1(or598ts), and determined that this mutation specifically disrupts the protein interaction between RSA-1 and the PP2A structural subunit, PAA-1. Through genetic screening, we identified a putative interface on the PAA-1 structural subunit that interacts with a defined region of RSA-1/B″. In the context of previously published results, these data propose a mechanism of how different PP2A B-regulatory subunit families can bind the same holoenzyme in a mutually exclusive manner, to perform specific tasks in vivo.

Structural Basis of PP2A Inhibition by Small t Antigen

PubMed Central

Cho, Uhn Soo; Morrone, Seamus; Sablina, Anna A; Arroyo, Jason D; Hahn, William C; Xu, Wenqing

2007-01-01

The SV40 small t antigen (ST) is a potent oncoprotein that perturbs the function of protein phosphatase 2A (PP2A). ST directly interacts with the PP2A scaffolding A subunit and alters PP2A activity by displacing regulatory B subunits from the A subunit. We have determined the crystal structure of full-length ST in complex with PP2A A subunit at 3.1 Å resolution. ST consists of an N-terminal J domain and a C-terminal unique domain that contains two zinc-binding motifs. Both the J domain and second zinc-binding motif interact with the intra-HEAT-repeat loops of HEAT repeats 3–7 of the A subunit, which overlaps with the binding site of the PP2A B56 subunit. Intriguingly, the first zinc-binding motif is in a position that may allow it to directly interact with and inhibit the phosphatase activity of the PP2A catalytic C subunit. These observations provide a structural basis for understanding the oncogenic functions of ST. PMID:17608567

In vitro extinction learning in Hermissenda: involvement of conditioned inhibition molecules

PubMed Central

Cavallo, Joel S.; Hamilton, Brittany N.; Farley, Joseph

2014-01-01

Extinction of a conditioned association is typically viewed as the establishment of new learning rather than the erasure of the original memory. However, recent research in the nudibranch, Hermissenda crassicornis (H.c.) demonstrated that extinction training (using repeated light-alone presentations) given 15 min, but not 23 h, after memory acquisition reversed both the cellular correlates of learning (enhanced Type B cell excitability) and the behavioral changes (reduced phototaxis) produced by associative conditioning (pairings of light, CS, and rotation, US). Here, we investigated the putative molecular signaling pathways that underlie this extinction in H.c. by using a novel in vitro protocol combined with pharmacological manipulations. After intact H.c. received either light-rotation pairings (Paired), random presentations of light and rotation (Random), or no stimulation (Untrained), B cells from isolated CNSs were recorded from during exposure to extinction training consisting of two series of 15 consecutive light-steps (LSs). When in vitro extinction was administered shortly (2 h, but not 24 h) after paired training, B cells from Paired animals showed progressive and robust declines in spike frequency by the 30th LS, while control cells (Random and Untrained) did not. We found that several molecules implicated in H.c. conditioned inhibitory (CI) learning, protein phosphatase 1 (PP1) and arachidonic acid (AA)/12-lipoxygenase (12-LOX) metabolites, also contributed to the spike frequency decreases produced by in vitro extinction. Protein phosphatase 2B (PP2B) also appeared to play a role. Calyculin A (PP1 inhibitor), cyclosporin A (PP2B inhibitor), and baicalein (a 12-LOX inhibitor) all blocked the spike frequency declines in Paired B cells produced by 30 LSs. Conversely, injection of catalytically-active PP1 (caPP1) or PP2B (caPP2B) into Untrained B cells partially mimicked the spike frequency declines observed in Paired cells, as did bath-applied AA, and occluded additional LS-produced reductions in spiking in Paired cells. PMID:25374517

PP2A activity is controlled by methylation and regulates oncoprotein expression in melanoma cells: a mechanism which participates in growth inhibition induced by chloroethylnitrosourea treatment.

PubMed

Guénin, Samuel; Schwartz, Laurent; Morvan, Daniel; Steyaert, Jean Marc; Poignet, Amandine; Madelmont, Jean Claude; Demidem, Aicha

2008-01-01

Protein phosphatase 2A (PP2A), an Akt pathway inhibitor, is considered to be activated by methylation of its catalytic subunit. Also PP2A downregulation was proposed to take part in carcinogenesis. Recently, PP2A activation was shown to be activated in response to DNA damage. To obtain further information on the role of PP2A in tumors and response to DNA damage, we investigated the relationship between PP2A methylation and activity, cell proliferation, Akt activation, c-Myc expression and PTEN activity in B16 melanoma cells untreated and after chloroethylnitrosourea (CENU) treatment. In untreated cells, okadaic acid, an antagonist of PP2A methylation, inhibited PP2A activity, stimulated cell proliferation, increased Akt activation and c-Myc expression. Xylulose-5-phosphate, an agonist of PP2A methylation, increased PP2A activity, decreased cell proliferation, Akt activation and c-Myc expression. However, both PP2A methylation modulators increased PTEN activity. During the response to CENU treatment, PP2A methylation and activity were strongly increased, Akt activation and c-Myc expression were decreased. However PTEN activity was increased. After tumor cell growth recovery, these modifications were moderately decreased. PP2A methylation was quantified and correlated positively with PP2A activity, and negatively with criteria for cell aggressiveness (cell proliferation, Akt activation, c-Myc expression). Based on these data, PP2A methylation status controls PP2A activity and oncoproteins expression and PP2A is strongly activated after CENU treatment thus partly explaining the growth inhibition in response to this agent. It follows that PP2A promethylating agents are potential candidates for anticancer drugs.

Suppressing Type 2C Protein Phosphatases Alters Fruit Ripening and the Stress Response in Tomato.

PubMed

Zhang, Yushu; Li, Qian; Jiang, Li; Kai, Wenbin; Liang, Bin; Wang, Juan; Du, Yangwei; Zhai, Xiawan; Wang, Jieling; Zhang, Yingqi; Sun, Yufei; Zhang, Lusheng; Leng, Ping

2018-01-01

Although ABA signaling has been widely studied in Arabidopsis, the roles of core ABA signaling components in fruit remain poorly understood. Herein, we characterize SlPP2C1, a group A type 2C protein phosphatase that negatively regulates ABA signaling and fruit ripening in tomato. The SlPP2C1 protein was localized in the cytoplasm close to AtAHG3/AtPP2CA. The SlPP2C1 gene was expressed in all tomato tissues throughout development, particularly in flowers and fruits, and it was up-regulated by dehydration and ABA treatment. SlPP2C1 expression in fruits was increased at 30 d after full bloom and peaked at the B + 1 stage. Suppression of SlPP2C1 expression significantly accelerated fruit ripening which was associated with higher levels of ABA signaling genes that are reported to alter the expression of fruit ripening genes involved in ethylene release and cell wall catabolism. SlPP2C1-RNAi (RNA interference) led to increased endogenous ABA accumulation and advanced release of ethylene in transgenic fruits compared with wild-type (WT) fruits. SlPP2C1-RNAi also resulted in abnormal flowers and obstructed the normal abscission of pedicels. SlPP2C1-RNAi plants were hypersensitized to ABA, and displayed delayed seed germination and primary root growth, and increased resistance to drought stress compared with WT plants. These results demonstrated that SlPP2C1 is a functional component in the ABA signaling pathway which participates in fruit ripening, ABA responses and drought tolerance. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Transcriptional regulation of SlPYL, SlPP2C, and SlSnRK2 gene families encoding ABA signal core components during tomato fruit development and drought stress.

PubMed

Sun, Liang; Wang, Yan-Ping; Chen, Pei; Ren, Jie; Ji, Kai; Li, Qian; Li, Ping; Dai, Sheng-Jie; Leng, Ping

2011-11-01

In order to characterize the potential transcriptional regulation of core components of abscisic acid (ABA) signal transduction in tomato fruit development and drought stress, eight SlPYL (ABA receptor), seven SlPP2C (type 2C protein phosphatase), and eight SlSnRK2 (subfamily 2 of SNF1-related kinases) full-length cDNA sequences were isolated from the tomato nucleotide database of NCBI GenBank. All SlPYL, SlPP2C, and SlSnRK2 genes obtained are homologous to Arabidopsis AtPYL, AtPP2C, and AtSnRK2 genes, respectively. Based on phylogenetic analysis, SlPYLs and SlSnRK2s were clustered into three subfamilies/subclasses, and all SlPP2Cs belonged to PP2C group A. Within the SlPYL gene family, SlPYL1, SlPYL2, SlPYL3, and SlPYL6 were the major genes involved in the regulation of fruit development. Among them, SlPYL1 and SlPYL2 were expressed at high levels throughout the process of fruit development and ripening; SlPYL3 was strongly expressed at the immature green (IM) and mature green (MG) stages, while SlPYL6 was expressed strongly at the IM and red ripe (RR) stages. Within the SlPP2C gene family, the expression of SlPP2C, SlPP2C3, and SlPP2C4 increased after the MG stage; SlPP2C1 and SlPP2C5 peaked at the B3 stage, while SlPP2C2 and SlPP2C6 changed little during fruit development. Within the SlSnRK2 gene family, the expression of SlSnRK2.2, SlSnRK2.3, SlSnRK2.4, and SlSnRK2C was higher than that of other members during fruit development. Additionally, most SlPYL genes were down-regulated, while most SlPP2C and SlSnRK2 genes were up-regulated by dehydration in tomato leaf.

Overexpression of a novel Arabidopsis PP2C isoform, AtPP2CF1, enhances plant biomass production by increasing inflorescence stem growth

PubMed Central

Sugimoto, Hiroki; Kondo, Satoshi; Tanaka, Tomoko; Imamura, Chie; Muramoto, Nobuhiko; Hattori, Etsuko; Ogawa, Ken’ichi; Mitsukawa, Norihiro; Ohto, Chikara

2014-01-01

In contrast to mammals, higher plants have evolved to express diverse protein phosphatase 2Cs (PP2Cs). Of all Arabidopsis thaliana PP2Cs, members of PP2C subfamily A, including ABI1, have been shown to be key negative regulators of abscisic acid (ABA) signalling pathways, which regulate plant growth and development as well as tolerance to adverse environmental conditions. However, little is known about the enzymatic and signalling roles of other PP2C subfamilies. Here, we report a novel Arabidopsis subfamily E PP2C gene, At3g05640, designated AtPP2CF1. AtPP2CF1 was dramatically expressed in response to exogenous ABA and was expressed in vascular tissues and guard cells, similar to most subfamily A PP2C genes. In vitro enzymatic activity assays showed that AtPP2CF1 possessed functional PP2C activity. However, yeast two-hybrid analysis revealed that AtPP2CF1 did not interact with PYR/PYL/RCAR receptors or three SnRK2 kinases, which are ABI1-interacting proteins. This was supported by homology-based structural modelling demonstrating that the putative active- and substrate-binding site of AtPP2CF1 differed from that of ABI1. Furthermore, while overexpression of ABI1 in plants induced an ABA-insensitive phenotype, Arabidopsis plants overexpressing AtPP2CF1 (AtPP2CF1oe) were weakly hypersensitive to ABA during seed germination and drought stress. Unexpectedly, AtPP2CF1oe plants also exhibited increased biomass yield, mainly due to accelerated growth of inflorescence stems through the activation of cell proliferation and expansion. Our results provide new insights into the physiological significance of AtPP2CF1 as a candidate gene for plant growth production and for potential application in the sustainable supply of plant biomass. PMID:25038254

Ferulic Acid Attenuates the Injury-Induced Decrease of Protein Phosphatase 2A Subunit B in Ischemic Brain Injury

PubMed Central

Koh, Phil-Ok

2013-01-01

Background Ferulic acid provides a neuroprotective effect during cerebral ischemia through its anti-oxidant function. Protein phosphatase 2A (PP2A) is a serine and threonine phosphatase that contributes broadly to normal brain function. This study investigated whether ferulic acid regulates PP2A subunit B in a middle cerebral artery occlusion (MCAO) animal model and glutamate toxicity-induced neuronal cell death. Methodology/Principal Findings MCAO was surgically induced to yield permanent cerebral ischemic injury in rats. The rats were treated with either vehicle or ferulic acid (100 mg/kg, i.v.) immediately after MCAO, and cerebral cortex tissues were collected 24 h after MCAO. A proteomics approach, RT-PCR, and Western blot analyses performed to identification of PP2A subunit B expression levels. Ferulic acid significantly reduced the MCAO-induced infarct volume of the cerebral cortex. A proteomics approach elucidated the reduction of PP2A subunit B in MCAO-induced animals, and ferulic acid treatment prevented the injury-induced reduction in PP2A subunit B levels. RT-PCR and Western blot analyses also showed that ferulic acid treatment attenuates the injury-induced decrease in PP2A subunit B levels. Moreover, the number of PP2A subunit B-positive cells was reduced in MCAO-induced animals, and ferulic acid prevented these decreases. In cultured neuronal cells, ferulic acid treatment protected cells against glutamate toxicity and prevented the glutamate-induced decrease in PP2A subunit B. Conclusions/Significance These results suggest that the maintenance of PP2A subunit B by ferulic acid in ischemic brain injury plays an important role for the neuroprotective function of ferulic acid. PMID:23349830

Global loss of Leucine Carboxyl Methyltransferase-1 causes severe defects in fetal liver hematopoiesis.

PubMed

Lee, Jocelyn A; Wang, Zhengqi; Sambo, Danielle; Bunting, Kevin D; Pallas, David C

2018-05-07

Leucine Carboxyl Methyltransferase-1 (LCMT-1) 3 methylates the carboxy-terminal leucine α-carboxyl group of the catalytic subunits of the protein phosphatase 2A (PP2A) subfamily of protein phosphatases, PP2Ac, PP4c, and PP6c. LCMT-1 differentially regulates the formation and function of a subset of the heterotrimeric complexes that PP2A and PP4 form with their regulatory subunits. Global LCMT-1 knockout causes embryonic lethality in mice, but LCMT-1 function in development is unknown. In the current study, we analyzed the effects of global LCMT-1 loss on embryonic development. LCMT-1 knockout causes loss of PP2Ac methylation, indicating that LCMT-1 is the sole PP2Ac methyltransferase. PP2A heterotrimers containing the Bα and Bδ B-type subunits are dramatically reduced in whole embryos, and the steady-state levels of PP2Ac and the PP2A structural A subunit are also down ~30%. Strikingly, global loss of LCMT-1 causes severe defects in fetal hematopoiesis and death by embryonic day 16.5 (E16.5). Fetal livers of homozygous lcmt-1 knockout embryos display hypocellularity, elevated apoptosis, and greatly reduced numbers of hematopoietic stem and progenitor cell-enriched Kit + Lin - Sca1 + (KLS) cells. The percent cycling cells and mitotic indexes of wild-type and lcmt-1 knockout fetal liver cells are similar, suggesting that hypocellularity may be due to a combination of apoptosis and/or defects in specification, self-renewal, or survival of stem cells. Indicative of a possible intrinsic defect in stem cells, non-competitive and competitive transplantation experiments reveal that lcmt-1 loss causes a severe multi-lineage hematopoietic repopulating defect. Therefore, this study reveals a novel role for LCMT-1 as a key player in fetal liver hematopoiesis. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

G-actin provides substrate-specificity to eukaryotic initiation factor 2α holophosphatases

PubMed Central

Chen, Ruming; Rato, Cláudia; Yan, Yahui; Crespillo-Casado, Ana; Clarke, Hanna J; Harding, Heather P; Marciniak, Stefan J; Read, Randy J; Ron, David

2015-01-01

Dephosphorylation of eukaryotic translation initiation factor 2a (eIF2a) restores protein synthesis at the waning of stress responses and requires a PP1 catalytic subunit and a regulatory subunit, PPP1R15A/GADD34 or PPP1R15B/CReP. Surprisingly, PPP1R15-PP1 binary complexes reconstituted in vitro lacked substrate selectivity. However, selectivity was restored by crude cell lysate or purified G-actin, which joined PPP1R15-PP1 to form a stable ternary complex. In crystal structures of the non-selective PPP1R15B-PP1G complex, the functional core of PPP1R15 made multiple surface contacts with PP1G, but at a distance from the active site, whereas in the substrate-selective ternary complex, actin contributes to one face of a platform encompassing the active site. Computational docking of the N-terminal lobe of eIF2a at this platform placed phosphorylated serine 51 near the active site. Mutagenesis of predicted surface-contacting residues enfeebled dephosphorylation, suggesting that avidity for the substrate plays an important role in imparting specificity on the PPP1R15B-PP1G-actin ternary complex. DOI: http://dx.doi.org/10.7554/eLife.04871.001 PMID:25774600

Suppressor mutations identify amino acids in PAA-1/PR65 that facilitate regulatory RSA-1/B″ subunit targeting of PP2A to centrosomes in C. elegans

PubMed Central

Lange, Karen I.; Heinrichs, Jeffrey; Cheung, Karen; Srayko, Martin

2013-01-01

Summary Protein phosphorylation and dephosphorylation is a key mechanism for the spatial and temporal regulation of many essential developmental processes and is especially prominent during mitosis. The multi-subunit protein phosphatase 2A (PP2A) enzyme plays an important, yet poorly characterized role in dephosphorylating proteins during mitosis. PP2As are heterotrimeric complexes comprising a catalytic, structural, and regulatory subunit. Regulatory subunits are mutually exclusive and determine subcellular localization and substrate specificity of PP2A. At least 3 different classes of regulatory subunits exist (termed B, B′, B″) but there is no obvious similarity in primary sequence between these classes. Therefore, it is not known how these diverse regulatory subunits interact with the same holoenzyme to facilitate specific PP2A functions in vivo. The B″ family of regulatory subunits is the least understood because these proteins lack conserved structural domains. RSA-1 (regulator of spindle assembly) is a regulatory B″ subunit required for mitotic spindle assembly in Caenorhabditis elegans. In order to address how B″ subunits interact with the PP2A core enzyme, we focused on a conditional allele, rsa-1(or598ts), and determined that this mutation specifically disrupts the protein interaction between RSA-1 and the PP2A structural subunit, PAA-1. Through genetic screening, we identified a putative interface on the PAA-1 structural subunit that interacts with a defined region of RSA-1/B″. In the context of previously published results, these data propose a mechanism of how different PP2A B-regulatory subunit families can bind the same holoenzyme in a mutually exclusive manner, to perform specific tasks in vivo. PMID:23336080

Uranium hydrogeochemical and stream sediment reconnaissance of the Durango NTMS quadrangle, Colorado

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dawson, H.E.; Weaver, T.A.

1979-01-01

During the spring and summer of 1976, 1518 water and 1604 waterborne sediment samples were collected from 1804 locations in the Durango NTMS quadrangle, Colorado. The samples obtained from this 19 940-km/sup 2/ area were analyzed at the Los Alamos Scientific Laboratory for total uranium. The uranium concentrations in waters ranged from less than the detectable limit of 0.2 ppB to 25.7 ppB, with a mean value of 0.84 ppB. The concentrations in sediments ranged from 1.0 ppM to 71.6 ppM, with a mean value of 4.2 ppM. Study of total water and total sediment populations indicated that both aremore » actually mixtures of several populations. Consequently, samples were chosen for discussion on the basis of their having conspicuously high uranium concentrations relative to surrounding background values. Thirty-four water samples (approximately 2.2% of the total water population) had uranium concentrations above 5.00 ppB, the highest of which were well water samples from the San Luis Valley. Thirty-seven sediment samples (approximately 2.3% of the total sediment population) had uranium concentrations above 12.0 ppM. The majority of these were taken from sites in Precambrian rocks, but several came from Paleozoic and Mesozoic strate and Tertiary volcanics. The uranium concentrations in sediment samples from areas of Precambrian rock were especially high and these areas may warrant further, more detailed investigations.« less

Aralkyl selenoglycosides and related selenosugars in acetylated form activate protein phosphatase-1 and -2A.

PubMed

Kónya, Zoltán; Bécsi, Bálint; Kiss, Andrea; Tamás, István; Lontay, Beáta; Szilágyi, László; Kövér, Katalin E; Erdődi, Ferenc

2018-05-01

Aralkyl and aryl selenoglycosides as well as glycosyl selenocarboxylate derivatives were assayed on the activity of protein phosphatase-1 (PP1) and -2A (PP2A) catalytic subunits (PP1c and PP2Ac) in search of compounds for PP1c and PP2Ac effectors. The majority of tested selenoglycosides activated both PP1c and PP2Ac by ∼2-4-fold in a phosphatase assay with phosphorylated myosin light chain substrate when the hydroxyl groups of the glycosyl moiety were acetylated, but they were without any effects in the non-acetylated forms. A peptide from the myosin phosphatase target subunit-1 (MYPT1 23-38 ) that included an RVxF PP1c-binding motif attenuated activation of PP1c by 2-Trifluoromethylbenzyl 2,3,4,6-tetra-O-acetyl-1-seleno-β-d-glucopyranoside (TFM-BASG) and 4-Bromobenzyl 2,3,4,6-tetra-O-acetyl-1-seleno-β-d-glucopyranoside (Br-BASG). MYPT1 23-38 stimulated PP2Ac and contributed to PP2Ac activation exerted by either Br-BASG or TFM-BASG. Br-BASG and TFM-BASG suppressed partially binding of PP1c to MYPT1 in surface plasmon resonance based binding experiments. Molecular docking predicted that the hydrophobic binding surfaces in PP1c for interaction with either the RVxF residues of PP1c-interactors or selenoglycosides are partially overlapped. Br-BASG and TFM-BASG caused a moderate increase in the phosphatase activity of HeLa cells in 1 h, and suppressed cell viability in 24 h incubations. In conclusion, our present study identified selenoglycosides as novel activators of PP1 and PP2A as well as provided insights into the structural background of their interactions establishing a molecular model for future design of more efficient phosphatase activator molecules. Copyright © 2018 Elsevier Ltd. All rights reserved.

Investigating interfacial phenomena in polypropylene/glass fiber composites

NASA Astrophysics Data System (ADS)

Toke, Jeffrey Michael

The adhesion in polypropylene (PP)/glass composites is low due to the non-polar, non-reactive characteristics of PP. When maleated PP (mPP) is added to the matrix, adhesion is improved. Understanding the mechanisms of this phenomenon is critical in maximizing the adhesion in PP/glass composites. The strength of adhesion in PP/glass composites was investigated using glass bead composites. A Near-IR spectroscopic technique was used to evaluate the chemical reactions in the interphase. Twelve different commercial grades of maleated PP (mPP) were tested. The range of maleic anydride (MAH) content was from 0.3 weight percent (wt%) to 2.4 wt%, with one sample at 10 wt%. These mPPs were blended with a commercial PP from Huntsman, P4C5Z-027 (PP), a 20 MFI (melt flow index) polymer with minimal additives, in concentrations ranging from 0 to 20 wt%. Bead composites of non-coated (NON) and gamma-APS-coated beads (APS) were made to compare the strength of the interphase in the composite systems. The bead volume fraction used was 25 volume percent (vol%). Three polymers with different MAH content and different viscosities were tested at 1, 5, 10 and 20 wt%. All of the mPPs were tested at 5 wt%. In general, the mPP composites all exhibited higher strength compared to the PP. Pukanszky's model for tensile strength was applied that included the strength of the unfilled matrix and the volume percent of the beads in a single factor, B. Comparison of all of the polymers at 5 wt% showed that there were four groupings of the mPPs. The polymers with MAH content greater than 1.5 wt% showed the strongest adhesion with B values of ˜2.5. All of these polymers had viscosities less than 100 Pa-s (180°C, 1 Hz angular frequency). The next group of polymers, with B ˜ 2, had MAH contents ranging from 0.8 to 1.2 wt%, with viscosities ranging from the 21 Pa-s to greater than 2300 Pa-s (180°C, 1 Hz angular frequency). The following group, with B ˜ 0.9, had anhydride concentrations of 0.6 and 0.7 wt%, and viscosities of 127 and 3800 Pa-s, respectively. Finally, there were several polymers with B ˜ 0.6 that were not significantly different than the unmodified PP. Viscosity and anhydride concentration showed competing effects in the mPP samples. Overall, increasing the concentration of anhydride increased adhesion, but viscosity is reduced in high MAH content mPPs. When the anhydride content was below 1.5 wt%, increased viscosity showed greater adhesion. (Abstract shortened by UMI.)

Overexpression of a novel Arabidopsis PP2C isoform, AtPP2CF1, enhances plant biomass production by increasing inflorescence stem growth.

PubMed

Sugimoto, Hiroki; Kondo, Satoshi; Tanaka, Tomoko; Imamura, Chie; Muramoto, Nobuhiko; Hattori, Etsuko; Ogawa, Ken'ichi; Mitsukawa, Norihiro; Ohto, Chikara

2014-10-01

In contrast to mammals, higher plants have evolved to express diverse protein phosphatase 2Cs (PP2Cs). Of all Arabidopsis thaliana PP2Cs, members of PP2C subfamily A, including ABI1, have been shown to be key negative regulators of abscisic acid (ABA) signalling pathways, which regulate plant growth and development as well as tolerance to adverse environmental conditions. However, little is known about the enzymatic and signalling roles of other PP2C subfamilies. Here, we report a novel Arabidopsis subfamily E PP2C gene, At3g05640, designated AtPP2CF1. AtPP2CF1 was dramatically expressed in response to exogenous ABA and was expressed in vascular tissues and guard cells, similar to most subfamily A PP2C genes. In vitro enzymatic activity assays showed that AtPP2CF1 possessed functional PP2C activity. However, yeast two-hybrid analysis revealed that AtPP2CF1 did not interact with PYR/PYL/RCAR receptors or three SnRK2 kinases, which are ABI1-interacting proteins. This was supported by homology-based structural modelling demonstrating that the putative active- and substrate-binding site of AtPP2CF1 differed from that of ABI1. Furthermore, while overexpression of ABI1 in plants induced an ABA-insensitive phenotype, Arabidopsis plants overexpressing AtPP2CF1 (AtPP2CF1oe) were weakly hypersensitive to ABA during seed germination and drought stress. Unexpectedly, AtPP2CF1oe plants also exhibited increased biomass yield, mainly due to accelerated growth of inflorescence stems through the activation of cell proliferation and expansion. Our results provide new insights into the physiological significance of AtPP2CF1 as a candidate gene for plant growth production and for potential application in the sustainable supply of plant biomass. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Intracellular uptake and behavior of two types zinc protoporphyrin (ZnPP) micelles, SMA-ZnPP and PEG-ZnPP as anticancer agents; unique intracellular disintegration of SMA micelles.

PubMed

Nakamura, Hideaki; Fang, Jun; Gahininath, Bharate; Tsukigawa, Kenji; Maeda, Hiroshi

2011-11-07

SMA-ZnPP and PEG-ZnPP are micellar drugs, encapsulating zinc protoporphyrin IX (ZnPP) with styrene maleic acid copolymer (SMA) and covalent conjugate of ZnPP with polyethylene glycol (PEG) respectively. Their intracellular uptake rate and subcellular localization were investigated. We found SMA-ZnPP showed higher and more efficient (about 2.5 times) intracellular uptake rate than PEG-ZnPP, although both SMA-ZnPP and PEG-ZnPP micelles were localized at endoplasmic reticulum (ER) and inhibited the target enzyme heme oxygenase 1 (HO-1) similarly. Both micellar ZnPP were taken up into the tumor cells by endocytosis. Furthermore SMA-ZnPP and PEG-ZnPP were examined for their drug releasing mechanisms. Liberation of ZnPP from the SMA micelle appears to depend on cellular amphiphilic components such as lecithin, while that for PEG-ZnPP depends on hydrolytic cleavage. These results indicate that these micelle formulations make water insoluble ZnPP to water soluble practical anticancer agents. Copyright © 2011 Elsevier B.V. All rights reserved.

Phosphatidic acid (PA) binds PP2AA1 to regulate PP2A activity and PIN1 polar localization.

PubMed

Gao, Hong-Bo; Chu, Yu-Jia; Xue, Hong-Wei

2013-09-01

Phospholipase D (PLD) exerts broad biological functions in eukaryotes through regulating downstream effectors by its product, phosphatidic acid (PA). Protein kinases and phosphatases, such as mammalian target of rapamycin (mTOR), Protein Phosphatase 1 (PP1) and Protein Phosphatase 2C (PP2C), are PA-binding proteins that execute crucial regulatory functions in both animals and plants. PA participates in many signaling pathways by modulating the enzymatic activity and/or subcellular localization of bound proteins. In this study, we demonstrated that PLD-derived PA interacts with the scaffolding A1 subunit of Protein Phosphatase 2A (PP2A) and regulates PP2A-mediated PIN1 dephosphorylation in Arabidopsis. Genetic and pharmacological studies showed that both PA and PP2A participate in the regulation of auxin distribution. In addition, both the phosphorylation status and polar localization of PIN1 protein were affected by PLD inhibitors. Exogenous PA triggered the membrane accumulation of PP2AA1 and enhanced the PP2A activity at membrane, while PLD inhibition resulted in the reduced endosomal localization and perinuclear aggregation of PP2AA1. These results demonstrate the important role of PLD-derived PA in normal PP2A-mediated PIN dephosphorylation and reveal a novel mechanism, in which PA recruits PP2AA1 to the membrane system and regulates PP2A function on membrane-targeted proteins. As PA and PP2A are conserved among eukaryotes, other organisms might use similar mechanisms to mediate multiple biological processes.

Efficacy of dietary spray dried plasma protein to mitigate the negative effects on performance of pigs fed diets with corn naturally contaminated with multiple mycotoxins.

PubMed

Weaver, A C; Campbell, J M; Crenshaw, J D; Polo, J; Kim, S W

2014-09-01

The ability of spray dried plasma protein (SDPP) to reduce the negative effects of multiple mycotoxins from naturally contaminated corn on weaned pig performance and health was investigated (n = 180; 6.84 ± 0.11 kg). For 12 d after weaning, pigs were fed phase 1 nursery diets with either 0% SDPP (PP0) or 6% SDPP (PP6). After 12 d, pigs were fed phase 2 diets for 3 wk. Pigs fed PP0 in phase 1 continued to be fed a phase 2 diet with no SDPP (PP0/PP0) or were fed a diet including corn naturally contaminated with multiple mycotoxins (M), labeled PP0/PP0M. Pigs fed SDPP in phase 1 were fed either a diet with no SDPP (PP6/PP0), a diet with M and no SDPP (PP6/PP0M), a diet with M and 3% SDPP (PP6/PP3M), or a diet with M and 6% SDPP (PP6/PP6M). During phase 1, pigs fed PP6 had increased (P < 0.05) ADG, ADFI, and G:F, whereas immunological parameters were not altered. During phase 2, pigs consuming PP0/PP0M had reduced ADG (P < 0.01) and ADFI (P < 0.05) in contrast to pigs fed PP0/PP0, whereas the performance of pigs fed PP6/PP0M was intermediate to pigs fed PP0/PP0M and PP6/PP0. The ADG and ADFI did not differ for pigs fed PP0/PP0M and PP6/PP0M during phase 2. Performance of pigs fed PP6/PP3M in contrast to pigs fed PP6/PP0M during phase 2 did not differ; however, these pigs had lower (P < 0.05) tumor necrosis factor α and tended (P = 0.094) to have lower DNA damage. During phase 2, ADG and ADFI of pigs fed PP6/PP6M did not differ from pigs fed PP6/PP0M, but G:F tended (P = 0.067) to be increased in pigs fed PP6/PP6M. Over the entire study period, pigs fed PP0/PP0M had reduced (P < 0.05) ADG and tended (P = 0.067) to have reduced ADFI. During this time, pigs fed PP6/PP0M tended to have greater ADG and ADFI (P = 0.093 and P = 0.067, respectively) compared with pigs fed PP0/PP0M. Overall, feeding a diet with SDPP improved growth performance and feed intake of young pigs directly after weaning. Feeding multiple M had a negative impact on growth performance of pigs during this trial. This response was more significant when pigs were not fed SDPP in phase 1. Overall, when combining phase 1 and 2 performance data, daily gain and feed intake tended to be reduced when pigs were not fed 6% SDPP in phase 1. This study indicates that the composition of diets fed immediately after weaning may be important for pigs that subsequently are under a M challenge.

Increased AβPP Processing in Familial Danish Dementia Patients

PubMed Central

Matsuda, Shuji; Tamayev, Robert; D’Adamio, Luciano

2013-01-01

An autosomal dominant mutation in the BRI2/ITM2B gene causes Familial Danish Dementia (FDD). We have generated a mouse model of FDD, called FDDKI, genetically congruous to the human disease. These mice carry one mutant and one wild type Bri2/Itm2b allele, like FDD patients. Analysis of FDDKI mice and samples from human patients has shown that the Danish mutation causes loss of Bri2 protein. FDDKI mice show synaptic plasticity and memory impairments. BRI2 is a physiological interactor of amyloid-β protein precursor (AβPP), a gene associated with Alzheimer’s disease, which inhibits processing of AβPP. AβPP/Bri2 complexes are reduced in synaptic membranes of FDDKI mice. Consequently, AβPP metabolites derived from processing of AβPP by β-, α-, and γ-secretases are increased in Danish dementia mice. AβPP haplodeficiency prevents memory and synaptic dysfunctions, consistent with a role for AβPP-metabolites in the pathogenesis of memory and synaptic deficits. This genetic suppression provides compelling evidence that AβPP and BRI2 functionally interact. Here, we have investigated whether AβPP processing is altered in FDD patients’ brain samples. We find that the levels of several AβPP metabolites, including Aβ, are significantly increased in the brain sample derived from an FDD patient. Our data are consistent with the findings in FDDKI mice, and support the hypothesis that the neurological effects of the Danish form of BRI2 are caused by toxic AβPP metabolites, suggesting that Familial Danish and Alzheimer’s dementias share common pathogenic mechanisms. PMID:21841249

Increased AβPP processing in familial Danish dementia patients.

PubMed

Matsuda, Shuji; Tamayev, Robert; D'Adamio, Luciano

2011-01-01

An autosomal dominant mutation in the BRI2/ITM2B gene causes Familial Danish Dementia (FDD). We have generated a mouse model of FDD, called FDDKI, genetically congruous to the human disease. These mice carry one mutant and one wild type Bri2/Itm2b allele, like FDD patients. Analysis of FDDKI mice and samples from human patients has shown that the Danish mutation causes loss of Bri2 protein. FDDKI mice show synaptic plasticity and memory impairments. BRI2 is a physiological interactor of amyloid-β protein precursor (AβPP), a gene associated with Alzheimer's disease, which inhibits processing of AβPP. AβPP/Bri2 complexes are reduced in synaptic membranes of FDDKI mice. Consequently, AβPP metabolites derived from processing of AβPP by β-, α-, and γ-secretases are increased in Danish dementia mice. AβPP haplodeficiency prevents memory and synaptic dysfunctions, consistent with a role for AβPP-metabolites in the pathogenesis of memory and synaptic deficits. This genetic suppression provides compelling evidence that AβPP and BRI2 functionally interact. Here, we have investigated whether AβPP processing is altered in FDD patients' brain samples. We find that the levels of several AβPP metabolites, including Aβ, are significantly increased in the brain sample derived from an FDD patient. Our data are consistent with the findings in FDDKI mice, and support the hypothesis that the neurological effects of the Danish form of BRI2 are caused by toxic AβPP metabolites, suggesting that Familial Danish and Alzheimer's dementias share common pathogenic mechanisms.

Essential requirement for PP2A inhibition by the oncogenic receptor c-KIT suggests PP2A reactivation as a strategy to treat c-KIT+ cancers

PubMed Central

Roberts, Kathryn G.; Smith, Amanda M.; McDougall, Fiona; Carpenter, Helen; Horan, Martin; Neviani, Paolo; Powell, Jason A.; Thomas, Daniel; Guthridge, Mark A.; Perrotti, Danilo; Sim, Alistair T.R.; Ashman, Leonie K.; Verrills, Nicole M.

2010-01-01

Oncogenic mutations of the receptor tyrosine kinase c-KIT play an important role in the pathogenesis of gastrointestinal stromal tumors (GIST), systemic mastocytosis, and some acute myeloid leukemias (AML). Whilst juxtamembrane mutations commonly detected in GIST are sensitive to tyrosine kinase inhibitors, the kinase domain mutations frequently encountered in systemic mastocytosis and AML confer resistance and are largely unresponsive to targeted inhibition by the existing agent imatinib. In this study we show that myeloid cells expressing activated c-KIT mutants that are imatinib-sensitive (V560G) or –resistant (D816V) can inhibit the tumor suppressor activity of protein phosphatase 2A (PP2A). This effect was associated with reduced expression of PP2A structural (A) and regulatory subunits (B55α; B56α; B56γ and B56δ). Overexpression of PP2A-Aα in D816V c-KIT cells induced apoptosis and inhibited proliferation. In addition, pharmacological activation of PP2A by FTY720 reduced proliferation, inhibited clonogenic potential and induced apoptosis of mutant c-KIT+ cells, whilst having no effect on WT c-KIT cells or empty vector controls. FTY720 treatment caused dephosphorylation of the D816V c-KIT receptor and its downstream signaling targets pAkt, pSTAT5 and pERK1/2. Additionally, in vivo administration of FTY720 delayed the growth of V560G and D816V c-KIT tumors, inhibited splenic and bone marrow infiltration, and prolonged survival. Our findings show that PP2A inhibition is essential for c-KIT-mediated tumorigenesis, and that reactivating PP2A may offer an attractive strategy to treat drug-resistant c-KIT+ cancers. PMID:20551067

Genomic characterization of bacteriophage vB_PcaP_PP2 infecting Pectobacterium carotovorum subsp. carotovorum, a new member of a proposed genus in the subfamily Autographivirinae.

PubMed

Lim, Jeong-A; Heu, Sunggi; Park, Jinwoo; Roh, Eunjung

2017-08-01

Bacteriophage vB_PcaP_PP2 (PP2) is a novel virulent phage that infects the plant-pathogenic bacterium Pectobacterium carotovorum subsp. carotovorum. PP2 phage has a 41,841-bp double-stranded DNA encoding 47 proteins, and it was identified as a member of the family Podoviridae by transmission electron microscopy. Nineteen of its open reading frames (ORFs) show homology to functional proteins, and 28 ORFs have been characterized as hypothetical proteins. PP2 phage is homologous to Cronobacter phage vB_CskP_GAP227 and Dev-CD-23823. Based on phylogenetic analysis, PP2 and its homologous bacteriophages form a new group within the subfamily Autographivirinae in the family Podoviridae, suggesting the need to establish a new genus. No lysogenic-cycle-related genes or bacterial toxins were identified.

Test of universal rise of hadronic total cross sections based on {pi}p, Kp and pp, pp scatterings

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ishida, Muneyuki; Igi, Keiji; Theoretical Physics Laboratory, RIKEN, Wako, Saitama 351-0198

Recently, there have been several evidences that the hadronic total cross section {sigma}{sub tot} is proportional to Blog{sup 2}s, which is consistent with the Froissart unitarity bound. The COMPETE Collaboration has further assumed {sigma}{sub tot}{approx_equal}Blog{sup 2}(s/s{sub 0})+Z to extend its universal rise with the common values of B and s{sub 0} for all hadronic scatterings to reduce the number of adjustable parameters. It was suggested that the coefficient B was universal in the arguments of the color glass condensate of QCD in recent years. However, there has been no rigorous proof yet based only on QCD. We attempt to investigatemore » the value of B for {pi}{sup {+-}}p, K{sup {+-}}p and pp, pp scatterings, respectively, through the search for the simultaneous best fit to the experimental {sigma}{sub tot} and {rho} ratios at high energies. The {sigma}{sub tot} at the resonance- and intermediate-energy regions has also been exploited as a duality constraint based on the special form of the finite-energy sum rule. We estimate the values of B, s{sub 0}, and Z individually for {pi}{sup {+-}}p, K{sup {+-}}p and pp, pp scatterings without using the universality hypothesis. It turns out that the values of B are mutually consistent within 1 standard deviation. It has to be stressed that we cannot obtain such a definite conclusion without the duality constraint. It is also interesting to note that the values of Z for {pi}p, Kp, and p(p)p approximately satisfy the ratio 2 ratio 2 ratio 3 predicted by the quark model. The obtained value of B for p(p)p is B{sub pp}=0.280{+-}0.015 mb, which predicts {sigma}{sub tot}{sup pp}=108.0{+-}1.9 mb and {rho}{sup pp}=0.131{+-}0.0025 at the LHC energy {radical}(s)=14 TeV.« less

Characterization of Phlebotomus papatasi peritrophins, and the role of PpPer1 in Leishmania major survival in its natural vector.

PubMed

Coutinho-Abreu, Iliano V; Sharma, Narinder K; Robles-Murguia, Maricela; Ramalho-Ortigao, Marcelo

2013-01-01

The peritrophic matrix (PM) plays a key role in compartmentalization of the blood meal and as barrier to pathogens in many disease vectors. To establish an infection in sand flies, Leishmania must escape from the endoperitrophic space to prevent excretion with remnants of the blood meal digestion. In spite of the role played regarding Leishmania survival, little is known about sand fly PM molecular components and structural organization. We characterized three peritrophins (PpPer1, PpPer2, and PpPer3) from Phlebotomus papatasi. PpPer1 and PpPer2 display, respectively, four and one chitin-binding domains (CBDs). PpPer3 on the other hand has two CBDs, one mucin-like domain, and a putative domain with hallmarks of a CBD, but with changes in key amino acids. Temporal and spatial expression analyses show that PpPer1 is expressed specifically in the female midgut after blood feeding. PpPer2 and PpPer3 mRNAs were constitutively expressed in midgut and hindgut, with PpPer3 also being expressed in Malpighian tubules. PpPer2 was the only gene expressed in developmental stages. Interestingly, PpPer1 and PpPer3 expression are regulated by Le. major infection. Recombinant PpPer1, PpPer2 and PpPer3 were obtained and shown to display similar biochemical profiles as the native; we also show that PpPer1 and PpPer2 are able to bind chitin. Knockdown of PpPer1 led to a 44% reduction in protein, which in spite of producing an effect on the percentage of infected sand flies, resulted in a 39% increase of parasite load at 48 h. Our data suggest that PpPer1 is a component for the P. papatasi PM and likely involved in the PM role as barrier against Le. major infection.

Cloning and sequence analysis of a full-length cDNA of SmPP1cb encoding turbot protein phosphatase 1 beta catalytic subunit

NASA Astrophysics Data System (ADS)

Qi, Fei; Guo, Huarong; Wang, Jian

2008-02-01

Reversible protein phosphorylation, catalyzed by protein kinases and phosphatases, is an important and versatile mechanism by which eukaryotic cells regulate almost all the signaling processes. Protein phosphatase 1 (PP1) is the first and well-characterized member of the protein serine/threonine phosphatase family. In the present study, a full-length cDNA encoding the beta isoform of the catalytic subunit of protein phosphatase 1(PP1cb), was for the first time isolated and sequenced from the skin tissue of flatfish turbot Scophthalmus maximus, designated SmPP1cb, by the rapid amplification of cDNA ends (RACE) technique. The cDNA sequence of SmPP1cb we obtained contains a 984 bp open reading frame (ORF), flanked by a complete 39 bp 5' untranslated region and 462 bp 3' untranslated region. The ORF encodes a putative 327 amino acid protein, and the N-terminal section of this protein is highly acidic, Met-Ala-Glu-Gly-Glu-Leu-Asp-Val-Asp, a common feature for PP1 catalytic subunit but absent in protein phosphatase 2B (PP2B). And its calculated molecular mass is 37 193 Da and pI 5.8. Sequence analysis indicated that, SmPP1cb is extremely conserved in both amino acid and nucleotide acid levels compared with the PP1cb of other vertebrates and invertebrates, and its Kozak motif contained in the 5'UTR around ATG start codon is GXXAXXGXX ATGG, which is different from mammalian in two positions A-6 and G-3, indicating the possibility of different initiation of translation in turbot, and also the 3'UTR of SmPP1cb is highly diverse in the sequence similarity and length compared with other animals, especially zebrafish. The cloning and sequencing of SmPP1cb gene lays a good foundation for the future work on the biological functions of PP1 in the flatfish turbot.

Hyperphosphorylation of PP2A in colorectal cancer and the potential therapeutic value showed by its forskolin-induced dephosphorylation and activation.

PubMed

Cristóbal, Ion; Rincón, Raúl; Manso, Rebeca; Madoz-Gúrpide, Juan; Caramés, Cristina; del Puerto-Nevado, Laura; Rojo, Federico; García-Foncillas, Jesús

2014-09-01

The tumor suppressor protein phosphatase 2A (PP2A) is frequently inactivated in human cancer and phosphorylation of its catalytic subunit (p-PP2A-C) at tyrosine-307 (Y307) has been described to inhibit this phosphatase. However, its molecular and clinical relevance in colorectal cancer (CRC) remains unclear. p-PP2A-C Y307 was determined by immunoblotting in 7 CRC cell lines and 35 CRC patients. CRC cells were treated with the PP2A activator forskolin alone or combined with the PP2A inhibitor okadaic acid, 5-fluorouracil and oxaliplatin. We examined cell growth, colonosphere formation, caspase activity and AKT and ERK activation. PP2A-C was found hyperphosphorylated in CRC cell lines. Forskolin dephosphorylated and activated PP2A, impairing proliferation and colonosphere formation, and inducing activation of caspase 3/7 and changes in AKT and ERK phosphorylation. Moreover, forskolin showed additive effects with 5-fluorouracil and oxaliplatin treatments. Analysis of p-PP2A-C Y307 in primary tumors confirmed the presence of this alteration in a subgroup of CRC patients. Our data show that PP2A-C hyperphosphorylation is a frequent event that contributes to PP2A inhibition in CRC. Antitumoral effects of forskolin-mediated PP2A activation suggest that the analysis of p-PP2A-C Y307 status could be used to identify a subgroup of patients who would benefit from treatments based on PP2A activators. Copyright © 2014 Elsevier B.V. All rights reserved.

The M Phase Kinase Greatwall (Gwl) Promotes Inactivation of PP2A/B55δ, a Phosphatase Directed Against CDK Phosphosites

PubMed Central

Castilho, Priscila V.; Williams, Byron C.; Mochida, Satoru; Zhao, Yong

2009-01-01

We have previously shown that Greatwall kinase (Gwl) is required for M phase entry and maintenance in Xenopus egg extracts. Here, we demonstrate that Gwl plays a crucial role in a novel biochemical pathway that inactivates, specifically during M phase, “antimitotic” phosphatases directed against phosphorylations catalyzed by cyclin-dependent kinases (CDKs). A major component of this phosphatase activity is heterotrimeric PP2A containing the B55δ regulatory subunit. Gwl is activated during M phase by Cdk1/cyclin B (MPF), but once activated, Gwl promotes PP2A/B55δ inhibition with no further requirement for MPF. In the absence of Gwl, PP2A/B55δ remains active even when MPF levels are high. The removal of PP2A/B55δ corrects the inability of Gwl-depleted extracts to enter M phase. These findings support the hypothesis that M phase requires not only high levels of MPF function, but also the suppression, through a Gwl-dependent mechanism, of phosphatase(s) that would otherwise remove MPF-driven phosphorylations. PMID:19793917

Molecular Investigations of the Structure and Function of the Protein Phosphatase 1:Spinophilin:Inhibitor-2 Heterotrimeric Complex

PubMed Central

Dancheck, Barbara; Ragusa, Michael J.; Allaire, Marc; Nairn, Angus C.; Page, Rebecca; Peti, Wolfgang

2011-01-01

Regulation of the major ser/thr phosphatase Protein Phosphatase 1 (PP1) is controlled by a diverse array of targeting and inhibitor proteins. Though many PP1 regulatory proteins share at least one PP1 binding motif, usually the RVxF motif, it was recently discovered that certain pairs of targeting and inhibitor proteins bind PP1 simultaneously to form PP1 heterotrimeric complexes. To date, structural information for these heterotrimeric complexes, and, in turn, how they direct PP1 activity is entirely lacking. Using a combination of NMR spectroscopy, biochemistry and small angle X-ray scattering (SAXS), we show that major structural rearrangements in both spinophilin (targeting) and Inhibitor-2 (I-2, inhibitor) are essential for the formation of the heterotrimeric PP1:spinophilin:I-2 (PSI) complex. The RVxF motif of I-2 is released from PP1 during the formation of PSI, making the less prevalent SILK motif of I-2 essential for complex stability. The release of the I-2 RVxF motif allows for enhanced flexibility of both I-2 and spinophilin in the heterotrimeric complex. In addition, we used inductively coupled plasma atomic emission spectroscopy to show that PP1 contains two metals in both heterodimeric complexes (PP1:spinophilin and PP1:I2) and PSI, demonstrating that PSI retains the biochemical characteristics of the PP1:I2 holoenzyme. Finally, we combined the NMR and biochemical data with SAXS and molecular dynamics simulations to generate a structural model of the full heterotrimeric PSI complex. Collectively, these data reveal the molecular events that enable PP1 heterotrimeric complexes to exploit both the targeting and inhibitory features of the PP1-regulatory proteins to form multi-functional PP1 holoenzymes. PMID:21218781

Negative regulation of protein phosphatase 2Cbeta by ISG15 conjugation.

PubMed

Takeuchi, Tomoharu; Kobayashi, Takayasu; Tamura, Shinri; Yokosawa, Hideyoshi

2006-08-07

ISG15, an interferon-upregulated ubiquitin-like protein, is covalently conjugated to various cellular proteins (ISGylation). In this study, we found that protein phosphatase 2Cbeta (PP2Cbeta), which functions in the nuclear factor kappaB (NF-kappaB) pathway via dephosphorylation of TGF-beta-activated kinase, was ISGylated, and analysis by NF-kappaB luciferase reporter assay revealed that PP2Cbeta activity was suppressed by co-expression of ISG15, UBE1L, and UbcH8. We determined the ISGylation sites of PP2Cbeta and constructed its ISGylation-resistant mutant. In contrast to the wild type, this mutant suppressed the NF-kappaB pathway even in the presence of ISG15, UBE1L, and UbcH8. Thus, we propose that ISGylation negatively regulates PP2Cbeta activity.

Acute toxic responses of the freshwater planarian, Dugesia dorotocephala, to methylmercury

DOE Office of Scientific and Technical Information (OSTI.GOV)

Best, J.B.; Morita, M.; Ragin, J.

1981-07-01

Toxic responses of planaria to various aquatic habitat concentrations of methylmercury chloride (MMC) were investigated. One hundred percent lethality occurred within 5 h in 2 ppM MMC, 24 h in 1 ppM MMC, and 5 days in 0.5 ppM MMC. No deaths occurred in 0.2 ppM MMC over a 10 day period, however, non-lethal toxic responses were observed. Varying degrees of head resorption, progressing caudally from the snout were observed. With continuing exposure, partial head regeneration and recovery toward more normal appearance occurred by 10 days. Teratogenic effects were observed in surgical decapitation experiments. Head regeneration was retarded in 0.1more » and 0.2 ppM MMC. Malformations, visible lesions, or gross behavioral abnormalities were produced by 2 week exposure of planaria to concentrations of 20 ppB MMC or lower. (RJC)« less

A SABATH Methyltransferase from the moss Physcomitrella patens catalyzes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Nan; Ferrer, Jean-Luc; Moon, Hong S

2012-01-01

Known SABATH methyltransferases, all of which were identified from seed plants, catalyze methylation of either the carboxyl group of a variety of low molecular weight metabolites or the nitrogen moiety of precursors of caffeine. In this study, the SABATH family from the bryophyte Physcomitrella patens was identified and characterized. Four SABATH-like sequences (PpSABATH1, PpSABATH2, PpSABATH3, and PpSABATH4) were identified from the P. patens genome. Only PpSABATH1 and PpSABATH2 showed expression in the leafy gametophyte of P. patens. Full-length cDNAs of PpSABATH1 and PpSABATH2 were cloned and expressed in soluble form in Escherichia coli. Recombinant PpSABATH1 and PpSABATH2 were tested formore » methyltransferase activity with a total of 75 compounds. While showing no activity with carboxylic acids or nitrogen-containing compounds, PpSABATH1 displayed methyltransferase activity with a number of thiols. PpSABATH2 did not show activity with any of the compounds tested. Among the thiols analyzed, PpSABATH1 showed the highest level of activity with thiobenzoic acid with an apparent Km value of 95.5 lM, which is comparable to those of known SABATHs. Using thiobenzoic acid as substrate, GC MS analysis indicated that the methylation catalyzed by PpSABATH1 is on the sulfur atom. The mechanism for S-methylation of thiols catalyzed by PpSABATH1 was partially revealed by homology-based structural modeling. The expression of PpSABATH1 was induced by the treatment of thiobenzoic acid. Further transgenic studies showed that tobacco plants overexpressing PpSABATH1 exhibited enhanced tolerance to thiobenzoic acid, suggesting that PpSABATH1 have a role in the detoxification of xenobiotic thiols.« less

A wheat (Triticum aestivum) protein phosphatase 2A catalytic subunit gene provides enhanced drought tolerance in tobacco.

PubMed

Xu, Chongyi; Jing, Ruilian; Mao, Xinguo; Jia, Xiaoyun; Chang, Xiaoping

2007-03-01

Multiple copies of genes encoding the catalytic subunit (c) of protein phosphatase 2A (PP2A) are commonly found in plants. For some of these genes, expression is up-regulated under water stress. The aim of this study was to investigate expression and characterization of TaPP2Ac-1 from Triticum aestivum, and to evaluate the effects of TaPP2Ac-1 on Nicotiana benthamiana in response to water stress. TaPP2Ac-1 cDNA was isolated from wheat by in silico identification and RT-PCR amplification. Transcript levels of TaPP2Ac-1 were examined in wheat responding to water deficit. Copy numbers of TaPP2Ac-1 in wheat genomes and subcellular localization in onion epidermal cells were studied. Enzyme properties of the recombinant TaPP2Ac-1 protein were determined. In addition, studies were carried out in tobacco plants with pCAPE2-TaPP2Ac-1 under water-deficit conditions. TaPP2Ac-1 cDNA was cloned from wheat. Transcript levels of TaPP2Ac-1 in wheat seedlings were up-regulated under drought condition. One copy for this TaPP2Ac-1 was present in each of the three wheat genomes. TaPP2Ac-1 fused with GFP was located in the nucleus and cytoplasm of onion epidermis cells. The recombinant TaPP2Ac-1 gene was over-expressed in Escherichia coli and encoded a functional serine/threonine phosphatase. Transgenic tobacco plants over-expressing TaPP2Ac-1 exhibited stronger drought tolerance than non-transgenic tobacco plants. Tobacco plants with pCAPE2-TaPP2Ac-1 appeared to be resistant to water deficit, as shown by their higher capacity to maintain leaf relative water content, leaf cell-membrane stability index, water-retention ability and water use efficiency under water stress. The results suggest that the physiological role of TaPP2Ac-1 is related to drought stress response, possibly through its involvement in drought-responding signal transduction pathways.

Nano-sized calcium phosphate particles for periodontal gene therapy.

PubMed

Elangovan, Satheesh; Jain, Shardool; Tsai, Pei-Chin; Margolis, Henry C; Amiji, Mansoor

2013-01-01

Growth factors such as platelet-derived growth factor (PDGF) have significantly enhanced periodontal therapy outcomes with a high degree of variability, mostly due to the lack of continual supply for a required period of time. One method to overcome this barrier is gene therapy. The aim of this in vitro study is to evaluate PDGF-B gene delivery in fibroblasts using nano-sized calcium phosphate particles (NCaPP) as vectors. NCaPP incorporating green fluorescent protein (NCaPP-GFP) and PDGF-B (NCaPP-PDGF-B) plasmids were synthesized using an established precipitation system and characterized using transmission electron microscopy and 1.2% agarose gel electrophoresis. Biocompatibility and transfection of the nanoplexes in fibroblasts were evaluated using cytotoxicity assay and florescence microscopy, respectively. Polymerase chain reaction and enzyme-linked immunosorbent assay were performed to evaluate PDGF-B transfection after different time points of treatments, and the functionality of PDGF-B transfection was evaluated using the cell proliferation assay. Synthesized NCaPP nanoplexes incorporating the genes of GFP and PDGF-B were spherical in shape and measured about 30 to 50 nm in diameter. Gel electrophoresis confirmed DNA incorporation and stability within the nanoplexes, and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium reagent assay demonstrated their biocompatibility in fibroblasts. In vitro transfection studies revealed a higher and longer lasting transfection after NCaPP-PDGF-B treatment, which lasted up to 96 hours. Significantly enhanced fibroblast proliferation observed in NCaPP-PDGF-B-treated cells confirmed the functionality of these nanoplexes. NCaPP demonstrated higher levels of biocompatibility and efficiently transfected PDGF plasmids into fibroblasts under described in vitro conditions.

The Neurospora crassa PP2A Regulatory Subunits RGB1 and B56 Are Required for Proper Growth and Development and Interact with the NDR Kinase COT1

PubMed Central

Shomin-Levi, Hila; Yarden, Oded

2017-01-01

COT1 is the founding member of the highly conserved nuclear Dbf2-related (NDR) Ser/Thr kinase family and plays a role in the regulation of polar growth and development in Neurospora crassa and other fungi. Changes in COT1 phosphorylation state have been shown to affect hyphal elongation, branching, and conidiation. The function of NDR protein kinases has been shown to be regulated by type 2A protein phosphatases (PP2As). PP2As are heterotrimers comprised of a catalytic and scaffolding protein along with an interchangeable regulatory subunit involved in determining substrate specificity. Inactivation of the N. crassa PP2A regulatory subunits rgb-1 and b56 conferred severe hyphal growth defects. Partial suppression of defects observed in the rgb-1RIP strain (but not in the Δb56 mutant) was observed in cot-1 phosphomimetic mutants, demonstrating that altering COT1 phosphorylation state can bypass, at least in part, the requirement of a functional RGB1 subunit. The functional fusion proteins RGB1::GFP and B56::GFP predominantly localized to hyphal tips and septa, respectively, indicating that their primary activity is in different cellular locations. COT1 protein forms exhibited a hyperphosphorylated gel migration pattern in an rgb-1RIP mutant background, similar to that observed when the fungus was cultured in the presence of the PP2A inhibitor cantharidin. COT1 was hypophosphorylated in a Δb56 mutant background, suggesting that this regulatory subunit may be involved in determining COT1 phosphorylation state, yet in an indirect manner. Reciprocal co-immunoprecipitation analyses, using tagged COT1, PPH1, RGB1, and B56 subunits established that these proteins physically interact. Taken together, our data determine the presence of a functional and physical link between PP2A and COT1 and show that two of the PP2A regulatory subunits interact with the kinase and determine COT1 phosphorylation state. PMID:28928725

Effects of bioDensity Training and Power Plate Whole-Body Vibration on Strength, Balance, and Functional Independence in Older Adults.

PubMed

Smith, Derek T; Judge, Stacey; Malone, Ashley; Moynes, Rebecca C; Conviser, Jason; Skinner, James S

2016-01-01

Reduced strength, balance, and functional independence diminish quality of life and increase health care costs. Sixty adults (82.2 ± 4.9 years) were randomized to a control or three 12-week intervention groups: bioDensity (bD); Power Plate (PP) whole-body vibration (WBV); or bD+PP. bD involved one weekly 5-s maximal contraction of four muscle groups. PP involved two 5-min WBV sessions. Primary outcomes were strength, balance, and Functional Independence Measure (FIM). No groups differed initially. Strength significantly increased 22-51% for three muscle groups in bD and bD+PP (P < .001), with no changes in control and PP. Balance significantly improved in PP and bD+PP but not in control or bD. bD, PP, and bD+PP differentially improved FIM self-care and mobility. Strength improvements from weekly 5-min sessions of bD may impart health/clinical benefits. Balance and leg strength improvements suggest WBV beneficially impacts fall risk and incidence. Improved FIM scores are encouraging and justify larger controlled trials on bD and bD+PP efficacy.

The relative hydrolytic reactivities of pyrophosphites and pyrophosphates.

PubMed

Mistry, Dharmit; Powles, Nicholas

2013-09-14

The pH-rate profiles for the hydrolysis of pyrophosphate (PP(V)) and pyrophosphite (PP(III), pyro-di-H-phosphonate) are a complex function of pH, reflecting the different ionic species and their relative reactivities. PP(III) is more reactive than PP(V) at all pHs and only PP(III) shows a hydroxide-ion reaction at high pH, so it is 10(10)-fold more reactive than PP(V) in 0.1 M NaOH. The pK(a2) of PP(III) ~0.44, so the dominant species at pH's > 1 is the di-anion PP(III)(2-). Although there is no observable (NMR or ITC) binding of Mg(2+) to the PP(III) di-anion there is a modest increase in the rate of hydrolysis of PP(III) by Mg(2+). PP(III) is neither a substrate nor an inhibitor of pyrophosphatase, the enzyme that efficiently catalyses the hydrolysis of PP(V).

Brachypodium distachyon BdPP2CA6 Interacts with BdPYLs and BdSnRK2 and Positively Regulates Salt Tolerance in Transgenic Arabidopsis

PubMed Central

Zhang, Fan; Wei, Qiuhui; Shi, Jiaochun; Jin, Xia; He, Yuan; Zhang, Yang; Luo, Qingchen; Wang, Yuesheng; Chang, Junli; Yang, Guangxiao; He, Guangyuan

2017-01-01

The phytohormone abscisic acid (ABA) is essential in plant responding to biotic and abiotic stresses. Although ABA signaling model is well established in Arabidopsis, ABA receptor PYL family and clade A PP2C subfamily are not yet characterized in monocot model plant Brachypodium distachyon. In this study, we identified 12 PYLs and 8 clade A PP2Cs from B. distachyon genome and successfully cloned 12 PYLs and 7 clade A PP2Cs. Bioinformatic and expression analyses showed that most of the identified genes respond to several signal molecules and abiotic stresses. Protein–protein interaction analysis revealed that many BdPYLs and BdPP2CAs participate in the classic ABA-PYL-PP2C-SnRK2 signaling pathway. A clade A PP2C, designated BdPP2CA6, interacted with BdPYL11 in the absence of ABA and localized in nucleus. Most clade A PP2C members from Arabidopsis showed negatively regulation in ABA signaling pathway, whereas BdPP2CA6-overexpression transgenic Arabidopsis showed ABA hypersensitive phenotype, resulting in enhanced stomatal closure and salinity tolerance. Our results indicate that BdPP2CA6 positively regulates ABA and stress signal pathway in transgenic Arabidopsis plant seedlings. PMID:28293246

Isolation of lactobacillus reuteri from Peyer's patches and their effects on sIgA production and gut microbiota diversity.

PubMed

Wang, Panpan; Li, Ya; Xiao, Hang; Shi, Yonghui; Le, Guo-Wei; Sun, Jin

2016-09-01

We previously reported that specific Lactobacillus reuteri colonized within mouse Peyer's patches (PP) effectively prevented high fat diet induced obesity and low-grade chronic inflammation. We further investigated the role of PP Lactobacillus reuteri on sIgA production in rats in this study. Lactobacilli were isolated from rat PP. All isolates were L. reuteri and belonged to three phenotypes according to amplified fragment length polymorphism analysis. Typical strains of two main clusters, PP1 and PP2, were used to treat control and vitamin A deficient (VAD) rats, respectively. The feeding of PP1 and PP2 affected sIgA and Lactobacillus diversity by strain-specific manner. Free sIgA was significantly increased by PP1 (p = 0.069) and PP2 (p < 0.05) in the control rats but not in the VAD rats. Only PP1 significantly changed PP Lactobacillus diversity in the control rats (p < 0.05). However, PP2 specifically changed ileal Lactobacillus diversity in both control and VAD rats. Fecal sIgA was correlated with PP Lactobacillus diversity (R(2) = 0.7958, p = 0.011). Modulation of sIgA production by PP L. reuteri of rat is dependent on vitamin A and change of Lactobacillus diversity in PP. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Malouli, Daniel; Hansen, Scott G.; Nakayasu, Ernesto S.

The tegument phosphoprotein pp65 (UL83) is the most abundant virion protein in human cytomegalovirus (HCMV). Since pp65 is immunodominant in persistently infected individuals, subunit vaccines against HCMV often include pp65 as T cell stimulatory component. Although HCMV pp65 is non-essential for viral growth in vitro it is thought to have an important role in primary and persistent infection since pp65 displays multiple immunomodulatory functions. To determine whether pp65 is required for infection and to evaluate its role in natural and vaccination-induced immunity we generated a rhesus CMV lacking both homologues, pp65a (Rh111) and pp65b (Rh112). Lack of pp65 resulted inmore » a slight growth defect in vitro and an increase of defective particle formation. However, most pp65-deleted virions in the supernatant were phenotypically normal and proteomics analysis revealed that the ratios of the remaining viral proteins were largely unchanged. RhCMV Δpp65ab was able to persistently infect CMV-negative rhesus macaques (RM) and to super-infect RM previously infected with CMV. To determine whether T cells against pp65 are essential for protection against CMV, we challenged Δpp65ab-infected animals with RhCMV ΔUS2-11, a viral recombinant that lacks inhibitors of MHC-I antigen presentation and is thus unable to overcome CMV-specific T cell immunity. Despite a complete lack of pp65-specific T cells, Δpp65ab protected against ΔUS2-11 challenge suggesting that pp65-specific T cells are not essential for T cell immunity against CMV. Using the same approach we further demonstrate that pp65b-specific T cells, induced by heterologous prime/boost vaccination, are not sufficient to protect against ΔUS2-11 challenge. Our data provides a new approach to test the efficacy of subunit vaccine candidates and suggest that pp65 vaccines are insufficient to induce a T cell response that recapitulates the protective effect of natural infection.« less

Transcriptional regulation of genes encoding ABA metabolism enzymes during the fruit development and dehydration stress of pear 'Gold Nijisseiki'.

PubMed

Dai, Shengjie; Li, Ping; Chen, Pei; Li, Qian; Pei, Yuelin; He, Suihuan; Sun, Yufei; Wang, Ya; Kai, Wenbin; Zhao, Bo; Liao, Yalan; Leng, Ping

2014-09-01

To investigate the contribution of abscisic acid (ABA) in pear 'Gold Nijisseiki' during fruit ripening and under dehydration stress, two cDNAs (PpNCED1 and PpNCED2) which encode 9-cis-epoxycarotenoid dioxygenase (NCED) (a key enzyme in ABA biosynthesis), two cDNAs (PpCYP707A1 and PpCYP707A2) which encode 8'-hydroxylase (a key enzyme in the oxidative catabolism of ABA), one cDNA (PpACS3) which encodes 1-aminocyclopropane-1-carboxylic acid (ACC), and one cDNA (PpACO1) which encodes ACC oxidase involved in ethylene biosynthesis were cloned from 'Gold Nijisseiki' fruit. In the pulp, peel and seed, expressions of PpNCED1 and PpNCED2 rose in two stages which corresponded with the increase of ABA levels. The expression of PpCYP707A1 dramatically declined after 60-90 days after full bloom (DAFB) in contrast to the changes of ABA levels during this period, while PpCYP707A2 stayed low during the whole development of fruit. Application of exogenous ABA at 100 DAFB increased the soluble sugar content and the ethylene release but significantly decreased the titratable acid and chlorophyll contents in fruits. When fruits harvested at 100 DAFB were stored in the laboratory (25 °C, 50% relative humidity), the ABA content and the expressions of PpNCED1/2 and PpCYP707A1 in the pulp, peel and seed increased significantly, while ethylene reached its highest value after the maximum peak of ABA accompanied with the expressions of PpACS3 and PpACO1. In sum the endogenous ABA may play an important role in the fruit ripening and dehydration of pear 'Gold Nijisseiki' and the ABA level was regulated mainly by the dynamics of PpNCED1, PpNCED2 and PpCYP707A1 at the transcriptional level. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

BUBR1 recruits PP2A via the B56 family of targeting subunits to promote chromosome congression

PubMed Central

Xu, Peng; Raetz, Elizabeth A.; Kitagawa, Mayumi; Virshup, David M.; Lee, Sang Hyun

2013-01-01

Summary BUBR1 is a mitotic phosphoprotein essential for the maintenance of chromosome stability by promoting chromosome congression and proper kinetochore–microtubule (K-fiber) attachment, but the underlying mechanism(s) has remained elusive. Here we identify BUBR1 as a binding partner of the B56 family of Protein Phosphatase 2A regulatory subunits. The interaction between BUBR1 and the B56 family is required for chromosome congression, since point mutations in BUBR1 that block B56 binding abolish chromosome congression. The BUBR1:B56-PP2A complex opposes Aurora B kinase activity, since loss of the complex can be reverted by inhibiting Aurora B. Importantly, we show that the failure of BUBR1 to recruit B56-PP2A also contributes to the chromosome congression defects found in cells derived from patients with the Mosaic Variegated Aneuploidy (MVA) syndrome. Together, we propose that B56-PP2A is a key mediator of BUBR1's role in chromosome congression and functions by antagonizing Aurora B activity at the kinetochore for establishing stable kinetochore–microtubule attachment at the metaphase plate. PMID:23789096

Protein Kinase C Controls Binding of Igo/ENSA Proteins to Protein Phosphatase 2A in Budding Yeast.

PubMed

Thai, Vu; Dephoure, Noah; Weiss, Amit; Ferguson, Jacqueline; Leitao, Ricardo; Gygi, Steven P; Kellogg, Douglas R

2017-03-24

Protein phosphatase 2A (PP2A) plays important roles in controlling mitosis in all eukaryotic cells. The form of PP2A that controls mitosis is associated with a conserved regulatory subunit that is called B55 in vertebrates and Cdc55 in budding yeast. The activity of this form of PP2A can be inhibited by binding of conserved Igo/ENSA proteins. Although the mechanisms that activate Igo/ENSA to bind and inhibit PP2A are well understood, little is known about how Igo/Ensa are inactivated. Here, we have analyzed regulation of Igo/ENSA in the context of a checkpoint pathway that links mitotic entry to membrane growth in budding yeast. Protein kinase C (Pkc1) relays signals in the pathway by activating PP2A Cdc55 We discovered that constitutively active Pkc1 can drive cells through a mitotic checkpoint arrest, which suggests that Pkc1-dependent activation of PP2A Cdc55 plays a critical role in checkpoint signaling. We therefore used mass spectrometry to determine how Pkc1 modifies the PP2A Cdc55 complex. This revealed that Pkc1 induces changes in the phosphorylation of multiple subunits of the complex, as well as dissociation of Igo/ENSA. Pkc1 directly phosphorylates Cdc55 and Igo/ENSA, and phosphorylation site mapping and mutagenesis indicate that phosphorylation of Cdc55 contributes to Igo/ENSA dissociation. Association of Igo2 with PP2A Cdc55 is regulated during the cell cycle, yet mutation of Pkc1-dependent phosphorylation sites on Cdc55 and Igo2 did not cause defects in mitotic progression. Together, the data suggest that Pkc1 controls PP2A Cdc55 by multiple overlapping mechanisms. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

SILAC-based phosphoproteomics reveals new PP2A-Cdc55-regulated processes in budding yeast.

PubMed

Baro, Barbara; Játiva, Soraya; Calabria, Inés; Vinaixa, Judith; Bech-Serra, Joan-Josep; de LaTorre, Carolina; Rodrigues, João; Hernáez, María Luisa; Gil, Concha; Barceló-Batllori, Silvia; Larsen, Martin R; Queralt, Ethel

2018-05-01

Protein phosphatase 2A (PP2A) is a family of conserved serine/threonine phosphatases involved in several essential aspects of cell growth and proliferation. PP2ACdc55 phosphatase has been extensively related to cell cycle events in budding yeast; however, few PP2ACdc55 substrates have been identified. Here, we performed a quantitative mass spectrometry approach to reveal new substrates of PP2ACdc55 phosphatase and new PP2A-related processes in mitotic arrested cells. We identified 62 statistically significant PP2ACdc55 substrates involved mainly in actin-cytoskeleton organization. In addition, we validated new PP2ACdc55 substrates such as Slk19 and Lte1, involved in early and late anaphase pathways, and Zeo1, a component of the cell wall integrity pathway. Finally, we constructed docking models of Cdc55 and its substrate Mob1. We found that the predominant interface on Cdc55 is mediated by a protruding loop consisting of residues 84-90, thus highlighting the relevance of these aminoacids for substrate interaction. We used phosphoproteomics of Cdc55-deficient cells to uncover new PP2ACdc55 substrates and functions in mitosis. As expected, several hyperphosphorylated proteins corresponded to Cdk1-dependent substrates, although other kinases' consensus motifs were also enriched in our dataset, suggesting that PP2ACdc55 counteracts and regulates other kinases distinct from Cdk1. Indeed, Pkc1 emerged as a novel node of PP2ACdc55 regulation, highlighting a major role of PP2ACdc55 in actin cytoskeleton and cytokinesis, gene ontology terms significantly enriched in the PP2ACdc55-dependent phosphoproteome.

Two ω-3 FADs Are Associated with Peach Fruit Volatile Formation

PubMed Central

Wang, Jiao-Jiao; Liu, Hong-Ru; Gao, Jie; Huang, Yu-Ji; Zhang, Bo; Chen, Kun-Song

2016-01-01

Aroma-related volatiles, together with sugars and acids, play an important role in determining fruit flavor quality. Characteristic volatiles of peach fruit are mainly derived from fatty acids such as linoleic acid (18:2) and linolenic acid (18:3). In the present study, six genes encoding fatty acid desaturases (FAD) were cloned, including two ω-6 FAD genes (PpFAD2, PpFAD6) and four ω-3 FAD genes (PpFAD3-1, PpFAD3-2, PpFAD7 and PpFAD8). Heterologous expression of peach FADs in tobacco plants showed that PpFAD3-1, and PpFAD3-2 significantly reduced contents of 18:2, and accumulated significant higher levels of 18:3. In the case of volatiles, transgenic plants produced lower concentrations of hexanal and higher levels of (E)-2-hexenal. Consequently, the ratio of the (E)-2-hexenal and hexanal was about 5- and 3-fold higher than that of wild type (WT) in PpFAD3-1 and PpFAD3-2 transformants, respectively. No significant changes in volatile profiles were observed in transgenic plants overexpressing the four other peach FAD genes. Real-time quantitative polymerase chain reaction (qPCR) analysis showed that ripe fruit had high PpFAD3-1 and low PpFAD3-2 transcript levels. In contrast, high PpFAD3-2 and low PpFAD3-1 transcript levels were observed in young fruit. These results indicate a temporal regulation of these two ω-3 FADs during development and ripening, influencing peach fruit volatile formation. PMID:27043529

Mutations in a new Arabidopsis cyclophilin disrupt its interaction with protein phosphatase 2A

NASA Technical Reports Server (NTRS)

Jackson, K.; Soll, D.; Evans, M. L. (Principal Investigator)

1999-01-01

The heterotrimeric protein phosphatase 2A (PP2A) is a component of multiple signaling pathways in eukaryotes. Disruption of PP2A activity in Arabidopsis is known to alter auxin transport and growth response pathways. We demonstrated that the regulatory subunit A of an Arabidopsis PP2A interacts with a novel cyclophilin, ROC7. The gene for this cyclophilin encodes a protein that contains a unique 30-amino acid extension at the N-terminus, which distinguishes the gene product from all previously identified Arabidopsis cyclophilins. Altered forms of ROC7 cyclophilin with mutations in the conserved DENFKL domain did not bind to PP2A. Unlike protein phosphatase 2B, PP2A activity in Arabidopsis extracts was not affected by the presence of the cyclophilin-binding molecule cyclosporin. The ROC7 transcript was expressed to high levels in all tissues tested. Expression of an ROC7 antisense transcript gave rise to increased root growth. These results indicate that cyclophilin may have a role in regulating PP2A activity, by a mechanism that differs from that employed for cyclophilin regulation of PP2B.

Structure- and Modeling-based Identification of the Adenovirus E4orf4 Binding Site in the Protein Phosphatase 2A B55α Subunit*

PubMed Central

Horowitz, Ben; Sharf, Rakefet; Avital-Shacham, Meirav; Pechkovsky, Antonina; Kleinberger, Tamar

2013-01-01

The adenovirus E4orf4 protein regulates the progression of viral infection and when expressed outside the context of the virus it induces nonclassical, cancer cell-specific apoptosis. All E4orf4 functions known to date require an interaction between E4orf4 and protein phosphatase 2A (PP2A), which is mediated through PP2A regulatory B subunits. Specifically, an interaction with the B55α subunit is required for induction of cell death by E4orf4. To gain a better insight into the E4orf4-PP2A interaction, mapping of the E4orf4 interaction site in PP2A-B55α has been undertaken. To this end we used a combination of bioinformatics analyses of PP2A-B55α and of E4orf4, which led to the prediction of E4orf4 binding sites on the surface of PP2A-B55α. Mutation analysis, immunoprecipitation, and GST pulldown assays based on the theoretical predictions revealed that the E4orf4 binding site included the α1 and α2 helices described in the B55α structure and involved at least three residues located in these helices facing each other. Loss of E4orf4 binding was accompanied by reduced contribution of the B55α mutants to E4orf4-induced cell death. The identified E4orf4 binding domain lies above the previously described substrate binding site and does not overlap it, although its location could be consistent with direct or indirect effects on substrate binding. This work assigns for the first time a functional significance to the α1,α2 helices of B55α, and we suggest that the binding site defined by these helices could also contribute to interactions between PP2A and some of its cellular regulators. PMID:23530045

Negative Regulation of Abscisic Acid Signaling by the Fagus sylvatica FsPP2C1 Plays A Role in Seed Dormancy Regulation and Promotion of Seed Germination1

PubMed Central

González-García, Mary Paz; Rodríguez, Dolores; Nicolás, Carlos; Rodríguez, Pedro Luis; Nicolás, Gregorio; Lorenzo, Oscar

2003-01-01

FsPP2C1 was previously isolated from beech (Fagus sylvatica) seeds as a functional protein phosphatase type-2C (PP2C) with all the conserved features of these enzymes and high homology to ABI1, ABI2, and PP2CA, PP2Cs identified as negative regulators of ABA signaling. The expression of FsPP2C1 was induced upon abscisic acid (ABA) treatment and was also up-regulated during early weeks of stratification. Furthermore, this gene was specifically expressed in ABA-treated seeds and was hardly detectable in vegetative tissues. In this report, to provide genetic evidence on FsPP2C1 function in seed dormancy and germination, we used an overexpression approach in Arabidopsis because transgenic work is not feasible in beech. Constitutive expression of FsPP2C1 under the cauliflower mosaic virus 35S promoter confers ABA insensitivity in Arabidopsis seeds and, consequently, a reduced degree of seed dormancy. Additionally, transgenic 35S:FsPP2C1 plants are able to germinate under unfavorable conditions, as inhibitory concentrations of mannitol, NaCl, or paclobutrazol. In vegetative tissues, Arabidopsis FsPP2C1 transgenic plants show ABA-resistant early root growth and diminished induction of the ABA-response genes RAB18 and KIN2, but no effect on stomatal closure regulation. Seed and vegetative phenotypes of Arabidopsis 35S:FsPP2C1 plants suggest that FsPP2C1 negatively regulates ABA signaling. The ABA inducibility of FsPP2C1 expression, together with the transcript accumulation mainly in seeds, suggest that it could play an important role modulating ABA signaling in beechnuts through a negative feedback loop. Finally, we suggest that negative regulation of ABA signaling by FsPP2C1 is a factor contributing to promote the transition from seed dormancy to germination during early weeks of stratification. PMID:12970481

Regulatory Subunit B′γ of Protein Phosphatase 2A Prevents Unnecessary Defense Reactions under Low Light in Arabidopsis1[W][OA

PubMed Central

Trotta, Andrea; Wrzaczek, Michael; Scharte, Judith; Tikkanen, Mikko; Konert, Grzegorz; Rahikainen, Moona; Holmström, Maija; Hiltunen, Hanna-Maija; Rips, Stephan; Sipari, Nina; Mulo, Paula; Weis, Engelbert; von Schaewen, Antje; Aro, Eva-Mari; Kangasjärvi, Saijaliisa

2011-01-01

Light is an important environmental factor that modulates acclimation strategies and defense responses in plants. We explored the functional role of the regulatory subunit B′γ (B′γ) of protein phosphatase 2A (PP2A) in light-dependent stress responses of Arabidopsis (Arabidopsis thaliana). The predominant form of PP2A consists of catalytic subunit C, scaffold subunit A, and highly variable regulatory subunit B, which determines the substrate specificity of PP2A holoenzymes. Mutant leaves of knockdown pp2a-b′γ plants show disintegration of chloroplasts and premature yellowing conditionally under moderate light intensity. The cell-death phenotype is accompanied by the accumulation of hydrogen peroxide through a pathway that requires CONSTITUTIVE EXPRESSION OF PR GENES5 (CPR5). Moreover, the pp2a-b′γ cpr5 double mutant additionally displays growth suppression and malformed trichomes. Similar to cpr5, the pp2a-b′γ mutant shows constitutive activation of both salicylic acid- and jasmonic acid-dependent defense pathways. In contrast to cpr5, however, pp2a-b′γ leaves do not contain increased levels of salicylic acid or jasmonic acid. Rather, the constitutive defense response associates with hypomethylation of DNA and increased levels of methionine-salvage pathway components in pp2a-b′γ leaves. We suggest that the specific B′γ subunit of PP2A is functionally connected to CPR5 and operates in the basal repression of defense responses under low irradiance. PMID:21571669

Src family kinases mediate the inhibition of substance P release in the rat spinal cord by μ-opioid receptors and GABA(B) receptors, but not α2 adrenergic receptors.

PubMed

Zhang, Guohua; Chen, Wenling; Marvizón, Juan Carlos G

2010-09-01

GABA(B) , μ-opioid and adrenergic α(2) receptors inhibit substance P release from primary afferent terminals in the dorsal horn. Studies in cell expression systems suggest that μ-opioid and GABA(B) receptors inhibit transmitter release from primary afferents by activating Src family kinases (SFKs), which then phosphorylate and inhibit voltage-gated calcium channels. This study investigated whether SFKs mediate the inhibition of substance P release by these three receptors. Substance P release was measured as neurokinin 1 receptor (NK1R) internalization in spinal cord slices and in vivo. In slices, NK1R internalization induced by high-frequency dorsal root stimulation was inhibited by the μ-opioid agonist DAMGO and the GABA(B) agonist baclofen. This inhibition was reversed by the SFK inhibitor PP1. NK1R internalization induced by low-frequency stimulation was also inhibited by DAMGO, but PP1 did not reverse this effect. In vivo, NK1R internalization induced by noxious mechanical stimulation of the hind paw was inhibited by intrathecal DAMGO and baclofen. This inhibition was reversed by intrathecal PP1, but not by the inactive PP1 analog PP3. PP1 produced no effect by itself. The α(2) adrenergic agonists medetomidine and guanfacine produced a small but statistically significant inhibition of NK1R internalization induced by low-frequency dorsal root stimulation. PP1 did not reverse the inhibition by guanfacine. These results show that SFKs mediate the inhibition of substance P release by μ-opioid and GABA(B) receptors, but not by α(2) receptors, which is probably mediated by the binding of G protein βγ subunits to calcium channels. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd. No claim to original US government works.

Utilization of Industrial Waste for the Production of Bio-Preservative from Bacillus licheniformis Me1 and Its Application in Milk and Milk-Based Food Products.

PubMed

Nithya, Vadakedath; Prakash, Maya; Halami, Prakash M

2018-06-01

The bio-preservative efficacy of a partially purified antibacterial peptide (ppABP) produced by Bacillus licheniformis Me1 in an economical medium developed using agro-industry waste was evaluated by direct application in milk and milk-based food products. The addition of ppABP in milk samples stored at 4 ± 2 °C and 28 ± 2 °C resulted in the growth inhibition of pathogens Listeria monocytogenes Scott A, Micrococcus luteus ATCC 9341, and Staphylococcus aureus FRI 722. The shelf life of milk samples with added ppABP increased to 4 days at 28 ± 2 °C, whereas curdling and off-odor were noticed in samples without ppABP. Furthermore, the milk samples with ppABP were sensorily acceptable. Antilisterial effect was also observed in cheese and paneer samples treated with ppABP. These results clearly indicate that the ppABP of B. licheniformis Me1 can be utilized as a bio-preservative to control the growth of spoilage and pathogenic bacteria, thereby reducing the risk of food-borne diseases.

KEY COMPARISON: CCQM-K21 Key Comparison Determination of pp’-DDT in fish oil

NASA Astrophysics Data System (ADS)

Webb, K. S.; Carter, D.; Wolff Briche, C. S. J.

2003-01-01

A key comparison on the determination of (pp'-dichlorodiphenyl) trichloroethane (pp'-DDT) in a fish oil matrix has been successfully completed. Nine NMIs participated in this key comparison and used the technique of isotope dilution gas-chromatography mass spectrometry (ID/GC/MS) for the determinations. Two samples (A and B) of fish oil were distributed to participants, each gravimetrically spiked with pp'-DDT. The KCRV for Sample A is 0.0743 +/- 0.0020 µg g-1 and that of Sample B is 0.1655 +/- 0.0014 µg g-1 of pp'-DDT in fish oil. The results for Sample A showed a RSD of 3.5%, the RSD for Sample B was within 1%. These results were an improvement over those of the corresponding pilot study (CCQM-P21), where at a mass fraction of pp'-DDT in fish oil of 0.311 µg g-1 the RSD was 2.6%. The compound pp'-DDT is a typical organochlorine pesticide and this key comparison has shown that NMIs have the ability to measure such compounds at levels typically found in the environment. The compound (pp'-dichlorodiphenyl) dichloroethylene (pp'-DDE), a metabolite of pp'-DDT, was the subject of a previous key comparison (CCQM-K5). The compound pp'-DDT is technically more challenging than that of pp'-DDE since it can decompose during the measurement procedure. Consequently the success of this key comparison, combined with that of CCQM-K5 demonstrates a broad measurement capability by NMIs for organochlorine compounds in the environment. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the Mutual Recognition Arrangement (MRA).

Overexpression of PP2A-C5 that encodes the catalytic subunit 5 of protein phosphatase 2A in Arabidopsis confers better root and shoot development under salt conditions

USDA-ARS?s Scientific Manuscript database

Protein phosphatase 2A (PP2A) is an enzyme consisting of three subunits: a scaffolding A subunit, a regulatory B subunit and a catalytic C subunit. PP2As were shown to play diverse roles in eukaryotes. In this study, the function of the Arabidopsis PP2A-C5 gene that encodes the catalytic subunit 5 o...

Okadaic acid overcomes the blocked cell cycle caused by depleting Cdc2-related kinases in Trypanosoma brucei

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li Ziyin; Tu Xiaoming; Wang, Ching C.

2006-11-01

Mitosis and cytokinesis are highly coordinated in eukaryotic cells. But procyclic-form Trypanosoma brucei under G1 or mitotic arrest is still capable of dividing, resulting in anucleate daughter cells (zoids). Okadaic acid (OKA), an inhibitor of protein phosphatases PP1 and PP2A, is known to inhibit kinetoplast replication and cell division yielding multinucleate cells with single kinetoplasts. However, when OKA was applied to cells arrested in G1 or G2/M phase via RNAi knockdown of specific cdc2-related kinases (CRKs), DNA synthesis and nuclear division were resumed without kinetoplast replication or cell division, resulting in multinucleate cells as in the wild type. Cells arrestedmore » in G2/M via depleting the mitotic cyclin CycB2 or an aurora B kinase homologue TbAUK1 were, however, not released by OKA treatment. The phenomenon is thus similar to the OKA activation of Cdc2 in Xenopus oocyte by inhibiting PP2A [Maton, et al., Differential regulation of Cdc2 and Aurora-A in Xenopus oocytes: a crucial role of phosphatase 2A. J. Cell Sci. 118 (2005) 2485-2494]. A simultaneous knockdown of the seven PP1s or the PP2A catalytic subunit in T. brucei by RNA interference did not, however, result in multinucleate cells. This could be explained by assuming a negative regulation, either directly or indirectly, of CRK by an OKA-sensitive phosphatase, which could be a PP2A as in the Xenopus oocyte and a positive regulation of kinetoplast replication by an OKA-susceptible protein(s). Test of a PP2A-specific inhibitor, fostriecin, on cells arrested in G2/M via CRK depletion or a knockdown of the PP2A catalytic subunit from the CRK-depleted cells both showed a partial lift of the G2/M block without forming multinucleate cells. These observations support the abovementioned assumption and suggest the presence of a novel OKA-sensitive protein(s) regulating kinetoplast replication that still remains to be identified.« less

Structure of the protein phosphatase 2A holoenzyme.

PubMed

Xu, Yanhui; Xing, Yongna; Chen, Yu; Chao, Yang; Lin, Zheng; Fan, Eugene; Yu, Jong W; Strack, Stefan; Jeffrey, Philip D; Shi, Yigong

2006-12-15

Protein Phosphatase 2A (PP2A) plays an essential role in many aspects of cellular physiology. The PP2A holoenzyme consists of a heterodimeric core enzyme, which comprises a scaffolding subunit and a catalytic subunit, and a variable regulatory subunit. Here we report the crystal structure of the heterotrimeric PP2A holoenzyme involving the regulatory subunit B'/B56/PR61. Surprisingly, the B'/PR61 subunit has a HEAT-like (huntingtin-elongation-A subunit-TOR-like) repeat structure, similar to that of the scaffolding subunit. The regulatory B'/B56/PR61 subunit simultaneously interacts with the catalytic subunit as well as the conserved ridge of the scaffolding subunit. The carboxyterminus of the catalytic subunit recognizes a surface groove at the interface between the B'/B56/PR61 subunit and the scaffolding subunit. Compared to the scaffolding subunit in the PP2A core enzyme, formation of the holoenzyme forces the scaffolding subunit to undergo pronounced conformational rearrangements. This structure reveals significant ramifications for understanding the function and regulation of PP2A.

Human cytomegalovirus carries serine/threonine protein phosphatases PP1 and a host-cell derived PP2A.

PubMed Central

Michelson, S; Turowski, P; Picard, L; Goris, J; Landini, M P; Topilko, A; Hemmings, B; Bessia, C; Garcia, A; Virelizier, J L

1996-01-01

Human cytomegalovirus (CMV), a herpesvirus, is an important cause of morbidity and mortality in immunocompromised patients. When studying hyper-immediate-early events after contact between CMV virions and the cell membrane, we observed a hypophosphorylation of cellular proteins within 10 min. This can be explained in part by our finding that purified CMV contains serine/threonine protein phosphatase activities. Biochemical analyses indicate that this protein phosphatase activity has all characteristics of type 1 and 2A protein phosphatases (PP1 and PP2A). Specifically, PP1 accounts for approximately 30% and PP2A accounts for the remaining 70% of the phosphorylase phosphatase activity found. CMV produced in astrocytoma cells stably expressing an amino-terminally tagged PP2A catalytic subunit contained tagged enzyme, thus demonstrating the cellular origin of CMV-associated PP2A. PP2A is specifically found inside the virus, associated with the nucleocapsid fraction. Western blot (immunoblot) analysis of purified virus revealed the presence of the catalytic subunits of PP2A and PP1. Furthermore, the catalytic subunit of PP2A appears to be complexed to the regulatory subunits PR65 and PR55, which is also the most abundant configuration of this enzyme found in the host cells. Incubation of virus with okadaic acid before contact of CMV with cells prevented hypophosphorylation of cellular proteins, thus demonstrating the role of CMV-associated phosphatases in this phenomenon. CMV can thus transport an active enzyme from one cell to another. PMID:8627658

Measurement of the ratio of inclusive cross sections sigma(pp going to Z+b-jet)/sigma(pp going to Z+jet) in the dilepton final states

NASA Astrophysics Data System (ADS)

Smith, Kenneth James

The inclusive production of b-jets with a Z boson is an important background to searches for the Higgs boson in associated ZH → llbb¯ production at the Fermilab Tevatron collider. This thesis describes the most precise measurement to date of the ratio of inclusive cross sections sigma( pp¯ → Z +b-jet)/sigma( pp¯ → Z+jet) when a Z boson decays into two electrons or muons. The measurement uses a data sample from pp¯ collisions at the center of mass energy s = 1.96 TeV corresponding to an integrated luminosity of 4.2 fb -1 collected by the D0 detector. The measured ratio sigma( Z + b-jet)/sigma(Z+jet) is 0.0187 +/- 0.0021(stat) +/- 0.0015(syst) for jets with transverse momentum pT > 20 GeV and pseudorapidity |eta| ≤2.5. The measurement is compared with the next-to-leading order theoretical predictions from MCFM and is found to be consistent within uncertainties.

Biosynthesis of allene oxides in Physcomitrella patens

PubMed Central

2012-01-01

Background The moss Physcomitrella patens contains C18- as well as C20-polyunsaturated fatty acids that can be metabolized by different enzymes to form oxylipins such as the cyclopentenone cis(+)-12-oxo phytodienoic acid. Mutants defective in the biosynthesis of cyclopentenones showed reduced fertility, aberrant sporophyte morphology and interrupted sporogenesis. The initial step in this biosynthetic route is the conversion of a fatty acid hydroperoxide to an allene oxide. This reaction is catalyzed by allene oxide synthase (AOS) belonging as hydroperoxide lyase (HPL) to the cytochrome P450 family Cyp74. In this study we characterized two AOS from P. patens, PpAOS1 and PpAOS2. Results Our results show that PpAOS1 is highly active with both C18 and C20-hydroperoxy-fatty acid substrates, whereas PpAOS2 is fully active only with C20-substrates, exhibiting trace activity (~1000-fold lower kcat/KM) with C18 substrates. Analysis of products of PpAOS1 and PpHPL further demonstrated that both enzymes have an inherent side activity mirroring the close inter-connection of AOS and HPL catalysis. By employing site directed mutagenesis we provide evidence that single amino acid residues in the active site are also determining the catalytic activity of a 9-/13-AOS – a finding that previously has only been reported for substrate specific 13-AOS. However, PpHPL cannot be converted into an AOS by exchanging the same determinant. Localization studies using YFP-labeled AOS showed that PpAOS2 is localized in the plastid while PpAOS1 may be found in the cytosol. Analysis of the wound-induced cis(+)-12-oxo phytodienoic acid accumulation in PpAOS1 and PpAOS2 single knock-out mutants showed that disruption of PpAOS1, in contrast to PpAOS2, results in a significantly decreased cis(+)-12-oxo phytodienoic acid formation. However, the knock-out mutants of neither PpAOS1 nor PpAOS2 showed reduced fertility, aberrant sporophyte morphology or interrupted sporogenesis. Conclusions Our study highlights five findings regarding the oxylipin metabolism in P. patens: (i) Both AOS isoforms are capable of metabolizing C18- and C20-derived substrates with different specificities suggesting that both enzymes might have different functions. (ii) Site directed mutagenesis demonstrated that the catalytic trajectories of 9-/13-PpAOS1 and PpHPL are closely inter-connected and PpAOS1 can be inter-converted by a single amino acid exchange into a HPL. (iii) In contrast to PpAOS1, PpAOS2 is localized in the plastid where oxylipin metabolism takes place. (iv) PpAOS1 is essential for wound-induced accumulation of cis(+)-12-oxo phytodienoic acid while PpAOS2 appears not to be involved in the process. (v) Knock-out mutants of neither AOS showed a deviating morphological phenotype suggesting that there are overlapping functions with other Cyp74 enzymes. PMID:23194461

The role of porcine reproductive and respiratory syndrome (PRRS) virus structural and non-structural proteins in virus pathogenesis.

PubMed

Music, Nedzad; Gagnon, Carl A

2010-12-01

Porcine reproductive and respiratory syndrome (PRRS) is an economically devastating viral disease affecting the swine industry worldwide. The etiological agent, PRRS virus (PRRSV), possesses a RNA viral genome with nine open reading frames (ORFs). The ORF1a and ORF1b replicase-associated genes encode the polyproteins pp1a and pp1ab, respectively. The pp1a is processed in nine non-structural proteins (nsps): nsp1α, nsp1β, and nsp2 to nsp8. Proteolytic cleavage of pp1ab generates products nsp9 to nsp12. The proteolytic pp1a cleavage products process and cleave pp1a and pp1ab into nsp products. The nsp9 to nsp12 are involved in virus genome transcription and replication. The 3' end of the viral genome encodes four minor and three major structural proteins. The GP(2a), GP₃ and GP₄ (encoded by ORF2a, 3 and 4), are glycosylated membrane associated minor structural proteins. The fourth minor structural protein, the E protein (encoded by ORF2b), is an unglycosylated membrane associated protein. The viral envelope contains two major structural proteins: a glycosylated major envelope protein GP₅ (encoded by ORF5) and an unglycosylated membrane M protein (encoded by ORF6). The third major structural protein is the nucleocapsid N protein (encoded by ORF7). All PRRSV non-structural and structural proteins are essential for virus replication, and PRRSV infectivity is relatively intolerant to subtle changes within the structural proteins. PRRSV virulence is multigenic and resides in both the non-structural and structural viral proteins. This review discusses the molecular characteristics, biological and immunological functions of the PRRSV structural and nsps and their involvement in the virus pathogenesis.

Changes in body composition in apparently healthy urban Indian women up to 3 years postpartum.

PubMed

Kajale, Neha A; Khadilkar, Anuradha V; Chiplonkar, Shashi A; Khadilkar, Vaman

2015-01-01

Dietary and life style practices differ in postpartum (PP) and nonpregnant Indian women. Effect of these practices on postpartum weight retention (PPWR) and development of cardio-metabolic risk (CMR) has been scarcely studied in urban women. Aims of this study were to (i) compare anthropometry, biochemical parameters and body composition up to 3 years PP (ii) effect of PPWR, dietary fat intake and physical activity on CMR factors. Cross-sectional, 300-fullterm, apparently healthy primi-parous women (28.6 ± 3.4 years) randomly selected. 128 women within 7-day of delivery (Group-A), 88 with 1-2 years (Group-B) and 84 with 3-4-year-old-children (Group-C) were studied. Anthropometry, sociodemographic status, physical activity, diet, clinical examination, biochemical tests, body composition, at total body (TB), by dual energy X-ray absorptiometry (GE-Lunar DPX) were collected. Women at 3-year PP showed higher weight retention (6.5[10] kg) than at 1-year (3.0[7] kg) (median [IQR]). Android fat % (central obesity) increased (P < 0.05) at 1-year PP (47 ± 10.0%) when compared to 1-week PP (44.3 ± 6.7%) and remained elevated at 3-year PP (45.6 ± 10.2%). Regression analysis revealed that at 1-year PP, increase in PPWR (Odd Ratio [OR] 1.8, 95% confidence interval [CI] = [1.2, 2.5], P < 0.001) and inactivity (OR 1.4, 95% CI= (0.97, 2.0), P < 0.1) were predictors for CMR. At 3-year PP, only PPWR was responsible for increase in CMR parameters (OR 1.6, 95% CI = (1.3, 2.3), P < 0.001) and not inactivity (P > 0.1). Postdelivery, low physical activity and higher PPWR may increase CMR in Indian women.

RSL genes are sufficient for rhizoid system development in early diverging land plants.

PubMed

Jang, Geupil; Yi, Keke; Pires, Nuno D; Menand, Benoît; Dolan, Liam

2011-06-01

Land plants are anchored to their substratum from which essential inorganic nutrients are taken up. These functions are carried out by a system of rhizoids in early diverging groups of land plants, such as mosses, liverworts and hornworts. Physcomitrella patens RHD SIX-LIKE1 (PpRSL1) and PpRSL2 transcription factors are necessary for rhizoid development in mosses. Similar proteins, AtRHD6 and AtRSL1, control the development of root hairs in Arabidopsis thaliana. Auxin positively regulates root hair development independently of AtRHD6 and AtRSL1 in A. thaliana but the regulatory interactions between auxin and PpRSL1 and PpRSL2 are unknown. We show here that co-expression of PpRSL1 and PpRSL2 is sufficient for the development of the rhizoid system in the moss P. patens; constitutive expression of PpRSL1 and PpRSL2 converts developing leafy shoot axes (gametophores) into rhizoids. During wild-type development, PpRSL1 and PpRSL2 are expressed in the specialized cells that develop rhizoids, indicating that cell-specific expression of PpRSL1 and PpRSL2 is sufficient to promote rhizoid differentiation during wild-type P. patens development. In contrast to A. thaliana, auxin promotes rhizoid development by positively regulating PpRSL1 and PpRSL2 activity in P. patens. This indicates that even though the same genes control the development of root hairs and rhizoids, the regulation of this transcriptional network by auxin is different in these two species. This suggests that auxin might have controlled the development of the first land plant soil anchoring systems that evolved 465 million years ago by regulating the expression of RSL genes and that this regulatory network has changed since mosses and angiosperms last shared a common ancestor.

Kinetic resolution of sec-alcohols catalysed by Candida antarctica lipase B displaying Pichia pastoris whole-cell biocatalyst.

PubMed

Zhang, Kun; Pan, Zhiyou; Diao, Zhoujian; Liang, Shuli; Han, Shuangyan; Zheng, Suiping; Lin, Ying

2018-03-01

Kinetic resolution of sec-alcohols is a green process with biocatalyst. Candida antarctica lipase B (CALB) displayed on Pichia pastoris cell-surface (Pp-CALB) was characterized in kinetic resolution of sec-alcohols with different structures. The reaction parameters including acyl donors, molar ratio of substrates, solvents and temperatures were examined with 2-octanol as model substrate. 47.4% molar conversion of 2-octanol and 99.7% ee p were obtained after a 5h reaction with Pp-CALB, and 90% of its original activity still remained after being reused for 10 cycles. Pp-CALB was then used to several sec-alcohols and it showed great enzymatic activity and enantioselectivity to all tested sec-alcohols, more than 93.1% of ee p . The enantioselective characteristics of Pp-CALB catalysed sec-alcohols with different structures were compared with Novozyme 435 which was almost the same. Solvent free system as one way of green chemistry was applied to Pp-CALB and Pp-CALB showed great catalytic activity and enantioselectivity. Pp-CALB was potential biocatalyst of high enzymatic activity and enantioselectivity using in resolution of sec-alcohols. Copyright © 2017. Published by Elsevier Inc.

Target Tracking Based Scene Analysis

DTIC Science & Technology

1984-08-01

1082 , pp 377-391. [21 S.T. Barnard and M.A. Fisch~ler, "Computational Stereo", Computing Surveys 14, 1082 , pp 553-572. 131 K.H. Bers, M. Bohner, and P...Braunlage/Harz. FRG, June 21 - July 2, 1082 Springer, Berlin, 1083. pp 10.1-124. [81 R.B. Cate, T.*1B. Dennis, J.T. Mallin, K.S. Nedelman, NEIL Trenchard, and...Institute on Pictorial Data Analysis, Bonas, France, August 1-12, 1082 ), Springer, Berlin, 1983. [181 G.R. Legters Jr. and T.Y. Young, "A Mathematical

The master Greatwall kinase, a critical regulator of mitosis and meiosis.

PubMed

Vigneron, Suzanne; Robert, Perle; Hached, Khaled; Sundermann, Lena; Charrasse, Sophie; Labbé, Jean-Claude; Castro, Anna; Lorca, Thierry

2016-01-01

Entry into mitosis requires the coordinated activation of various protein kinases and phosphatases that together activate sequential signaling pathways allowing entry, progression and exit of mitosis. The limiting step is thought to be the activation of the mitotic Cdk1-cyclin B kinase. However, this model has recently evolved with new data showing that in addition to the Cdk1-cyclin B complex, Greatwall (Gwl) kinase is also required to enter into and maintain mitosis. This new concept proposes that entry into mitosis is now based on the combined activation of both kinases Cdk1-cyclin B and Gwl, the former promoting massive phosphorylation of mitotic substrates and the latter inhibiting PP2A-B55 phosphatase responsible for dephosphorylation of these substrates. Activated Gwl phosphorylates both Arpp19 and ENSA, which associate and inhibit PP2A-B55. This pathway seems relatively well conserved from yeast to humans, although some differences appear based on models or techniques used. While Gwl is activated by phosphorylation, its inactivation requires dephosphorylation of critical residues. Several phosphatases such as PP1, PP2A-B55 and FCP1 are required to control the dephosphorylation and inactivation of Gwl and a properly regulated mitotic exit. Gwl has also been reported to be involved in cancer processes and DNA damage recovery. These new findings support the idea that the Gwl-Arpp19/ENSA-PP2A-B55 pathway is essential to achieve an efficient division of cells and to maintain genomic stability.

Structure of a Protein Phosphatase 2A Holoenzyme: Insights into B55-Mediated Tau Dephosphorylation

PubMed Central

Xu, Yanhui; Chen, Yu; Zhang, Ping; Jeffrey, Philip D.; Shi, Yigong

2009-01-01

Summary Protein phosphatase 2A (PP2A) regulates many essential aspects of cellular physiology. Members of the regulatory B/B55/PR55 family are thought to play a key role in the dephosphorylation of Tau, whose hyperphosphorylation contributes to Alzheimer's disease. The underlying mechanisms of the PP2A-Tau connection remain largely enigmatic. Here, we report the complete reconstitution of a Tau dephosphorylation assay and the crystal structure of a heterotrimeric PP2A holoenzyme involving the regulatory subunit Bα. We show that Bα specifically and markedly facilitates dephosphorylation of the phosphorylated Tau in our reconstituted assay. The Bα subunit comprises a seven-bladed β propeller, with an acidic, substrate-binding groove located in the center of the propeller. The β propeller latches onto the ridge of the PP2A scaffold subunit with the help of a protruding β hairpin arm. Structure-guided mutagenesis studies revealed the underpinnings of PP2A-mediated dephosphorylation of Tau. PMID:18922469

PP2ARts1 is a master regulator of pathways that control cell size

PubMed Central

Zapata, Jessica; Dephoure, Noah; MacDonough, Tracy; Yu, Yaxin; Parnell, Emily J.; Mooring, Meghan; Gygi, Steven P.; Stillman, David J.

2014-01-01

Cell size checkpoints ensure that passage through G1 and mitosis occurs only when sufficient growth has occurred. The mechanisms by which these checkpoints work are largely unknown. PP2A associated with the Rts1 regulatory subunit (PP2ARts1) is required for cell size control in budding yeast, but the relevant targets are unknown. In this paper, we used quantitative proteome-wide mass spectrometry to identify proteins controlled by PP2ARts1. This revealed that PP2ARts1 controls the two key checkpoint pathways thought to regulate the cell cycle in response to cell growth. To investigate the role of PP2ARts1 in these pathways, we focused on the Ace2 transcription factor, which is thought to delay cell cycle entry by repressing transcription of the G1 cyclin CLN3. Diverse experiments suggest that PP2ARts1 promotes cell cycle entry by inhibiting the repressor functions of Ace2. We hypothesize that control of Ace2 by PP2ARts1 plays a role in mechanisms that link G1 cyclin accumulation to cell growth. PMID:24493588

Retinoic Acid Protects Cardiomyocytes from High Glucose-Induced Apoptosis via Inhibition of Sustained Activation of NF-κB Signaling

PubMed Central

Nizamutdinova, Irina T.; Guleria, Rakeshwar S.; Singh, Amar B.; Kendall, Jonathan A.; Baker, Kenneth M.; Pan, Jing

2012-01-01

We have previously shown that retinoic acid (RA) has protective effects on high glucose (HG)-induced cardiomyocyte apoptosis. To further elucidate the molecular mechanisms of RA effects, we determined the interaction between nuclear factor (NF)-κB and RA signaling. HG induced a sustained phosphorylation of IKK/IκBα and transcriptional activation of NF-κB in cardiomyocytes. Activated NF-κB signaling has an important role in HG-induced cardiomyocyte apoptosis and gene expression of interleukin-6 (IL-6), tumor necrosis factor (TNF)-α and monocyte chemoattractant protein-1 (MCP-1). All-trans RA (ATRA) and LGD1069, through activation of RAR/RXR-mediated signaling, inhibited the HG-mediated effects in cardiomyocytes. The inhibitory effect of RA on NF-κB activation was mediated through inhibition of IKK/IκBα phosphorylation. ATRA and LGD1069 treatment promoted protein phosphatase 2A (PP2A) activity, which was significantly suppressed by HG stimulation. The RA effects on IKK and IκBα were blocked by okadaic acid or silencing the expression of PP2Ac-subunit, indicating that the inhibitory effect of RA on NF-κB is regulated through activation of PP2A and subsequent dephosphorylation of IKK/IκBα. Moreover, ATRA and LGD1069 reversed the decreased PP2A activity and inhibited the activation of IKK/IκBα and gene expression of MCP-1, IL-6 and TNF-α in the hearts of Zucker diabetic fatty rats. In summary, our findings suggest that the suppressed activation of PP2A contributed to sustained activation of NF-κB in HG-stimulated cardiomyocytes; and that the protective effect of RA on hyperglycemia-induced cardiomyocyte apoptosis and inflammatory responses is partially regulated through activation of PP2A and suppression of NF-κB-mediated signaling and downstream targets. PMID:22718360

Books Noted

NASA Astrophysics Data System (ADS)

Walsh, Edward J.

1999-10-01

The Colloidal Domain: Where Physics, Chemistry, Biology, and Technology Meet, 2nd edition

D. Fennell Evans and Hakan Wennerstroem. Advances in Interfacial Engineering Series. Wiley-VCH: New York, 1999. xl + 632 pp. ISBN 0-471-24247-0. 89.95.

Commercial Nuclear Power: Assuring Safety for the Future

Charles B. Ramsey and Mohammed Modarres. Wiley-Interscience: New York, 1998. xxviii + 508 pp. ISBN 0-471-29186-2. 79.95.

Advances in Medicinal Chemistry, Vol. 4

Bruce E. Maryanoff and Allen B. Reitz, Eds. JAI Press: Stamford, CT, 1999. ISBN 1-7623-0064-7. 109.50.

Advances in Strained and Interesting Organic Molecules, Vol. 7

Brian Halton, Ed. JAI Press: Stamford, CT, 1999. xii + 259 pp. ISBN 0-7623-0530-4. 109.50.

Advances in Electron Transfer Chemistry, Vol. 6

Patrick S. Mariano, Ed. JAI Press: Stamford, CT, 1999. x + 171 pp. ISBN 0-7623-0213-5. 109.50.

Automating Science and Engineering Laboratories with Visual Basic

Mark F. Russo and Martin M. Echols. Wiley-Interscience Series on Laboratory Automation. Wiley-Interscience: New York, 1999. xx + 355 pp. ISBN 0-471-25493-2. 49.95.

Plantwide Process Control

Kelvin T. Erickson and John L. Hedrick. Wiley Series in Chemical Engineering. Wiley-Interscience: New York, 1999. xii + 547 pp. ISBN 0-471-17835-7. 89.95.

Heme Peroxidases

H. Brian Dunford. Wiley-VCH: New York, 1999. xiii + 507 pp. ISBN 0-471-24244-6. 195.00.

Industrial Ecology: Environmental Chemistry and Hazardous Wastes

Stanley E. Manahan. Lewis: Boca Raton, FL, 1999. 318 pp. ISBN 1-56670-381-6. 69.95.

Reviews in Computational Chemistry, Vol. 13

Kenny B. Lipkowitz and Donald B. Boyd. Wiley-VCH: New York, 1999. xxxiii + 426 pp. ISBN 0-471-33135-x. 135.00.

Surfaces, Interfaces, and Colloids: Principles and Applications, 2nd edition

Drew Myers. Wiley-VCH: New York, 1999. xx + 501 pp. ISBN 0-471-33060-4. 94.95.

Onium Ions

George A. Olah, Kenneth K. Laali, Qi Wang, and G. K. Surya Prakash. Wiley-Interscience: New York, 1998. xv + 509 pp. ISBN 0-471-14877-6. 110.00.

Environmental Soil and Water Chemistry: Principles and Applications V. P. Evangelou. Wiley-Interscience: New York, 1998. xix + 564 pp. ISBN 0-471-16515-8. 79.95.

1001 Chemicals in Everyday Products, 2nd edition

Grace Ross Lewis. Wiley-Interscience: New York, 1999. x + 388 pp. ISBN 0-471-29212-5. 39.95.

Organic Coatings: Science and Technology, 2nd edition

Zeno W. Wicks Jr., Frank N. Jones, and S. Peter Pappas. Wiley-Interscience: New York, 1999. xxi + 630 pp. ISBN 0-471-24507-0. 125.00.

Progress in Inorganic Chemistry, Vol. 48

Kenneth D. Karlin, Ed. Wiley-Interscience: New York, 1999. vi + 603 pp. ISBN 0-471-32623-2. 145.00.

Occupational Biomechanics, 3rd edition

Don B. Chaffin, Gunnar B. Andersson, and Bernard J. Martin. Wiley-Interscience: New York, 1999. xvii + 579 pp. ISBN 0-471-24697-2. 69.95.

Advances in Photochemistry, Vol. 25

Douglas C. Neckers, David H. Volman, and Gunther Von Bünau. Wiley-Interscience: New York, 1999. xi + 238 pp. ISBN 0-471-32708-5. 110.00.

Distillation

Johann G. Stichlmair and James R. Fair. Wiley-VCH: New York, 1998. xiii + 524 pp. ISBN 0-471-25241-7. 94.95.

Ammonia - Principles and Industrial Practice

Maz Appl. Wiley-VCH: New York, 1999. ix + 301 pp. ISBN 3-527-29593-3. 160.00.

Precursor-Derived Ceramics: Synthesis, Structure, and High-Temperature Mechanical Properties

Fritz Aldinger, Fumihiro Wakai, and Joachim Bill, Eds. Wiley-VCH: New York, 1999. xv + 298 pp. ISBN 3-527-29814-2. 180.00.

Advances in Sonochemisty, Vol. 5

Timothy J. Mason. JAI Press: Stamford, CT, 1999. xi + 311 pp. ISBN 0-7623-0331-x. 109.50.

Fluid Metals: The Liquid-Vapor Transition of Metals

Friedrich Hensel and William W. Warren Jr. Princeton University Press: Princeton, NJ. 1999. xvii + 243 pp. ISBN 0-691-05830-x. 69.50.

Direct Phasing in Crystallography: Fundamentals and Applications

Carmelo Giacovazzo. Oxford University Press: New York, 1999. xxiii + 767 pp. ISBN 0-19-850072-6. 140.00.

Practical Environmental Analysis

M. Radojevic and V. N. Bashkin. Royal Society of Chemistry: Cambridge, UK. 1999. xx + 466 pp. ISBN 0-85404-594-5. £32.00.

Advances in Dendritic Macromolecules, Vol. 4 George R. Newkome, Ed. JAI Press: Stamford, CT, 1999. x + 207 pp. ISBN 0-7623-0347-6. 109.50.

Advances in Quantitative Structure-Property Relationships, Vol. 2

Marvin Charton. JAI Press: Stamford, CT, 1999. ix + 257 pp. ISBN 0-7623-0067-1. 109.50.

Pesticide Residues in Foods: Methods, Techniques, and Regulations

W. George Fong, H. Anson Moye, James N. Seiber, and John P. Toth. Chemical Analysis, Vol. 151.Wiley-Interscience: New York, 1999. xiv + 358 pp. ISBN 0-471-57400-7. $84.95.

Abscisic Acid (ABA ) Promotes the Induction and Maintenance of Pear (Pyrus pyrifolia White Pear Group) Flower Bud Endodormancy

PubMed Central

Li, Jianzhao; Xu, Ying; Niu, Qingfeng; He, Lufang; Teng, Yuanwen; Bai, Songling

2018-01-01

Dormancy is an adaptive mechanism that allows temperate deciduous plants to survive unfavorable winter conditions. In the present work, we investigated the possible function of abscisic acid (ABA) on the endodormancy process in pear. The ABA content increased during pear flower bud endodormancy establishment and decreased towards endodormancy release. In total, 39 putative genes related to ABA metabolism and signal transductions were identified from pear genome. During the para- to endodormancy transition, PpNCED-2 and PpNCED-3 had high expression levels, while PpCYP707As expression levels were low. However, during endodormancy, the expression of PpCYP707A-3 sharply increased with increasing cold accumulation. At the same time, the ABA content of pear buds declined, and the percentage of bud breaks rapidly increased. On the other hand, the expression levels of PpPYLs, PpPP2Cs, PpSnRK2s, and PpABI4/ABI5s were also changed during the pear flower bud dormancy cycle. Furthermore, exogenous ABA application to para-dormant buds significantly reduced the bud breaks and accelerated the transition to endodormancy. During the whole treatment time, the expression level of PpPP2C-12 decreased to a greater extent in ABA-treated buds than in control. However, the expression levels of PpSnRK2-1, PpSnRK2-4, and PpABI5-1 were higher in ABA-treated buds. Our results indicated that PpCYP707A-3 and PpNCEDs play pivotal roles on the regulation of endodormancy release, while ABA signal transduction pathway also appears to be involved in the process. The present work provided the basic information about the function of ABA-related genes during pear flower bud dormancy process. PMID:29361708

Peach MYB7 activates transcription of the proanthocyanidin pathway gene encoding leucoanthocyanidin reductase, but not anthocyanidin reductase

PubMed Central

Zhou, Hui; Lin-Wang, Kui; Liao, Liao; Gu, Chao; Lu, Ziqi; Allan, Andrew C.; Han, Yuepeng

2015-01-01

Proanthocyanidins (PAs) are a group of natural phenolic compounds that have a great effect on both flavor and nutritious value of fruit. It has been shown that PA synthesis is regulated by R2R3-MYB transcription factors (TFs) via activation of PA-specific pathway genes encoding leucoanthocyanidin reductase and anthocyanidin reductase. Here, we report the isolation and characterization of a MYB gene designated PpMYB7 in peach. The peach PpMYB7 represents a new group of R2R3-MYB genes regulating PA synthesis in plants. It is able to activate transcription of PpLAR1 but not PpANR, and has a broader selection of potential bHLH partners compared with PpMYBPA1. Transcription of PpMYB7 can be activated by the peach basic leucine-zipper 5 TF (PpbZIP5) via response to ABA. Our study suggests a transcriptional network regulating PA synthesis in peach, with the results aiding the understanding of the functional divergence between R2R3-MYB TFs in plants. PMID:26579158

Structure and function of the PP2A-shugoshin interaction

PubMed Central

Xu, Zheng; Cetin, Bulent; Anger, Martin; Cho, Uhn Soo; Helmhart, Wolfgang; Nasmyth, Kim; Xu, Wenqing

2009-01-01

SUMMARY Accurate chromosome segregation during mitosis and meiosis depends on shugoshin proteins that prevent precocious dissociation of cohesin from centromeres. Shugoshins associate with PP2A, which is thought to de-phosphorylate cohesin and thereby prevent cleavage by separase during meiosis I. A crystal structure of a complex between a fragment of human Sgo1 and an AB’C PP2A holoenzyme reveals that Sgo1 forms a homodimeric parallel coiled-coil that docks simultaneously onto PP2A’s C and B’ subunits. Sgo1 homo-dimerization is a pre-requisite for PP2A binding. While hSgo1 interacts only with the AB’C holoenzymes, its relative Sgo2 interacts with all PP2A forms and may thus lead to dephosphorylation of distinct substrates. Mutant shugoshin proteins defective in the binding of PP2A cannot protect centromeric cohesin from separase during meiosis I or support the spindle assembly checkpoint in yeast. Finally, we provide evidence that PP2A’s recruitment to chromosomes may be sufficient to protect cohesin from separase in mammalian oocytes. PMID:19716788

High-energy pp and pp-bar forward elastic scattering and total cross sections

DOE Office of Scientific and Technical Information (OSTI.GOV)

Block, M.M.; Cahn, R.N.

1985-04-01

The present status of elastic pp and pp-bar scattering in the high-energy domain is reviewed, with emphasis on the forward and near-forward regions. The experimental techniques for measuring sigma/sub tot/, rho, and B are discussed, emphasizing the importance of the region in which the nuclear and Coulomb scattering interfere. The impact-parameter representation is exploited to give simple didactic demonstrations of important rigorous theorems based on analyticity, and to illuminate the significance of the slope parameter B and the curvature parameter C. Models of elastic scattering are discussed, and a criterion for the onset of ''asymptopia'' is given. A critique ofmore » dispersion relations is presented. Simple analytic functions are used to fit simultaneously the real and imaginary parts of forward scattering amplitudes for both pp and pp-bar, obtained from experimental data for sigma/sub tot/ and rho. It is found that a good fit can be obtained using only five parameters (with a cross section rising as ln/sup 2/s), over the energy range 5 < ..sqrt..s < 62 GeV. The possibilities that (a) the cross section rises only as lns, (b) the cross section rises only locally as ln/sup 2/s, and eventually goes to a constant value, and (c) the cross-section difference between pp and pp-bar does not vanish as s..-->..infinity are examined critically. The nuclear slope parameters B are also fitted in a model-independent fashion. Examination of the fits reveals a new regularity of the pp-bar and the pp systems.« less

Supplementation of Pork Patties with Bovine Plasma Protein Hydrolysates Augments Antioxidant Properties and Improves Quality.

PubMed

Seo, Hyun-Woo; Seo, Jin-Kyu; Yang, Han-Sul

2016-01-01

This study investigated the effects of bovine plasma protein (PP) hydrolysates on the antioxidant and quality properties of pork patties during storage. Pork patties were divided into 4 groups: without butylated hydroxytoluene (BHT) and PP hydrolysates (control), 0.02% BHT (T1), 1% PP hydrolysates (T2), and 2% PP hydrolysates (T3). Pork patty supplemented with PP hydrolysates had higher pH values and lower weight loss during cooking than the control patties. Results showed that lightness and hardness both decreased upon the addition of PP hydrolysates. All samples containing BHT and PP hydrolysates had reduced TBARS and peroxide values during storage. In particular, 2% PP hydrolysates were more effective in delaying lipid oxidation than were the other treatments. It was concluded that treatment with 2% PP hydrolysates can enhance the acceptance of pork patty.

Phrase Length and Prosody in On-Line Ambiguity Resolution

ERIC Educational Resources Information Center

Webman-Shafran, Ronit; Fodor, Janet Dean

2016-01-01

We investigated the processing of ambiguous double-PP constructions in Hebrew. Selection restrictions forced the first prepositional phrase (PP1) to attach low, but PP2 could attach maximally high to VP or maximally low to the NP inside PP1. A length contrast in PP2 was also examined. This construction affords more potential locations for prosodic…

Synthesis and coordinating ability of an anionic cobaltabisdicarbollide ligand geometrically analogous to BINAP.

PubMed

Rojo, Isabel; Teixidor, Francesc; Viñas, Clara; Kivekäs, Raikko; Sillanpää, Reijo

2004-10-25

The anionic chelating ligand [1,1'-(PPh2)2-3,3'-Co(1,2-C2B9H10)2]- has been synthesized from [3,3'-Co(1,2-C2B9H11)2]- in very good yield in a one-pot process with an easy work-up procedure. The coordinating ability of this ligand has been studied with Group 11 metal ions (Ag, Au) and with transition-metal ions (Pd, Rh). The two dicarbollide halves of the [1,1'-(PPh2)2-3,3'-Co(1,2-C2B9H10)2]- ligand can swing about one axis in a manner analogous to the constituent parts of BINAP and ferrocenyl phosphine derivatives. All these ligands function as hinges, with the most important property in relation to the coordination requirements of the metal being the PP distance. [1,1'-(PPh2)2-3,3'-Co(1,2-C2B9H10)2]-, BINAP, ferrocenyl phosphine derivatives, and other hinge ligands present a range of different PP separations, and consequently different coordination spheres and dispositions around metal cations. To account for these differences, the equation Dphi2 = D02 + 4 R2cos2(90-phi/2) has been developed. It relates the PP distance (Dphi) in a complex with the minimum PP distance (D0) that is characteristic of the hinge-type ligand.

Effects of low-level SO/sub 2/ on Usnes hirta and Parmelia chlorachroa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eversman, S.

1978-01-01

Respiration rates of Usnea hirta (l.) wigg, and Parmelia chlorochroa tuck exposed in the field to SO/sub 2/ fumigation decreased significantly, compared to control rates, within 30 days at 94 ppB SO/sub 2/ and within 60 days at 33 ppB. Nearly 100% of the algal cells were plasmolyzed within 60 days. The respiration rates of P. chlorochora samples were not significantly different from those of conrol samples after 60 days of exposure to 18 ppB SO/sub 2/. The respiration rates of U. hirta samples were significantly less than those of control samples after 96 days of exposure to 18 ppBmore » SO/sub 2/. A significantly greater percentage of the algal cells were plasmolyzed in U. hirta and P. chlorochroa, compared to control samples, after 31 days of exposure to 18 ppB. Damage to the lichens was more obvious and occurred faster than damage to adjacent vascular vegetation.« less

Therapeutic potential of a dual mTORC1/2 inhibitor for the prevention of posterior capsule opacification: An in vitro study.

PubMed

Feng, Hao; Yang, Zhibo; Bai, Xue; Yang, Meirong; Fang, Yuan; Zhang, Xiaonan; Guo, Qiqiang; Ning, Hong

2018-04-01

Mammalian target of rapamycin (mTOR) serves a central role in regulating cell growth and survival, and has been demonstrated to be involved in the pathological progression of posterior capsule opacification (PCO). In the present study, the potency of PP242, a novel dual inhibitor of mTOR complex 1/2 (mTORC1/2), in the suppression of the growth of human lens epithelial cells (HLECs) was investigated. Using a Cell Counting Kit‑8 and a wound healing assay, it was demonstrated that PP242 inhibited the proliferation and migration of HLECs. In addition, western blot analysis indicated that PP242 completely inhibited mTORC1 and mTORC2 downstream signaling activities, whereas rapamycin only partially inhibited mTORC1 activity within LECs. Furthermore, PP242 treatment led to an upregulation of the expression levels of p53 and B cell lymphoma‑2 (Bcl‑2)‑associated X and downregulation of Bcl‑2. In addition, flow cytometric analysis demonstrated that PP242 induced the cell cycle arrest at the G0/G1 phase, which may have caused apoptosis and induced autophagy within the LECs. The results of the present study suggested that administration of PP242 may potentially offer a novel therapeutic approach for the prevention of PCO.

The Ndc80 complex targets Bod1 to human mitotic kinetochores

PubMed Central

2017-01-01

Regulation of protein phosphatase activity by endogenous protein inhibitors is an important mechanism to control protein phosphorylation in cells. We recently identified Biorientation defective 1 (Bod1) as a small protein inhibitor of protein phosphatase 2A containing the B56 regulatory subunit (PP2A-B56). This phosphatase controls the amount of phosphorylation of several kinetochore proteins and thus the establishment of load-bearing chromosome-spindle attachments in time for accurate separation of sister chromatids in mitosis. Like PP2A-B56, Bod1 directly localizes to mitotic kinetochores and is required for correct segregation of mitotic chromosomes. In this report, we have probed the spatio-temporal regulation of Bod1 during mitotic progression. Kinetochore localization of Bod1 increases from nuclear envelope breakdown until metaphase. Phosphorylation of Bod1 at threonine 95 (T95), which increases Bod1's binding to and inhibition of PP2A-B56, peaks in prometaphase when PP2A-B56 localization to kinetochores is highest. We demonstrate here that kinetochore targeting of Bod1 depends on the outer kinetochore protein Ndc80 and not PP2A-B56. Crucially, Bod1 depletion functionally affects Ndc80 phosphorylation at the N-terminal serine 55 (S55), as well as a number of other phosphorylation sites within the outer kinetochore, including Knl1 at serine 24 and 60 (S24, S60), and threonine T943 and T1155 (T943, T1155). Therefore, Ndc80 recruits a phosphatase inhibitor to kinetochores which directly feeds forward to regulate Ndc80, and Knl1 phosphorylation, including sites that mediate the attachment of microtubules to kinetochores. PMID:29142109

First observation of a baryonic Bc+ decay.

PubMed

Aaij, R; Adeva, B; Adinolfi, M; Affolder, A; Ajaltouni, Z; Akar, S; Albrecht, J; Alessio, F; Alexander, M; Ali, S; Alkhazov, G; Alvarez Cartelle, P; Alves, A A; Amato, S; Amerio, S; Amhis, Y; An, L; Anderlini, L; Anderson, J; Andreassen, R; Andreotti, M; Andrews, J E; Appleby, R B; Aquines Gutierrez, O; Archilli, F; Artamonov, A; Artuso, M; Aslanides, E; Auriemma, G; Baalouch, M; Bachmann, S; Back, J J; Badalov, A; Baldini, W; Barlow, R J; Barschel, C; Barsuk, S; Barter, W; Batozskaya, V; Battista, V; Bay, A; Beaucourt, L; Beddow, J; Bedeschi, F; Bediaga, I; Belogurov, S; Belous, K; Belyaev, I; Ben-Haim, E; Bencivenni, G; Benson, S; Benton, J; Berezhnoy, A; Bernet, R; Bettler, M-O; van Beuzekom, M; Bien, A; Bifani, S; Bird, T; Bizzeti, A; Bjørnstad, P M; Blake, T; Blanc, F; Blouw, J; Blusk, S; Bocci, V; Bondar, A; Bondar, N; Bonivento, W; Borghi, S; Borgia, A; Borsato, M; Bowcock, T J V; Bowen, E; Bozzi, C; Brambach, T; van den Brand, J; Bressieux, J; Brett, D; Britsch, M; Britton, T; Brodzicka, J; Brook, N H; Brown, H; Bursche, A; Busetto, G; Buytaert, J; Cadeddu, S; Calabrese, R; Calvi, M; Calvo Gomez, M; Campana, P; Campora Perez, D; Carbone, A; Carboni, G; Cardinale, R; Cardini, A; Carson, L; Carvalho Akiba, K; Casse, G; Cassina, L; Castillo Garcia, L; Cattaneo, M; Cauet, Ch; Cenci, R; Charles, M; Charpentier, Ph; Chefdeville, M; Chen, S; Cheung, S-F; Chiapolini, N; Chrzaszcz, M; Ciba, K; Cid Vidal, X; Ciezarek, G; Clarke, P E L; Clemencic, M; Cliff, H V; Closier, J; Coco, V; Cogan, J; Cogneras, E; Cojocariu, L; Collins, P; Comerma-Montells, A; Contu, A; Cook, A; Coombes, M; Coquereau, S; Corti, G; Corvo, M; Counts, I; Couturier, B; Cowan, G A; Craik, D C; Cruz Torres, M; Cunliffe, S; Currie, R; D'Ambrosio, C; Dalseno, J; David, P; David, P N Y; Davis, A; De Bruyn, K; De Capua, S; De Cian, M; De Miranda, J M; De Paula, L; De Silva, W; De Simone, P; Decamp, D; Deckenhoff, M; Del Buono, L; Déléage, N; Derkach, D; Deschamps, O; Dettori, F; Di Canto, A; Dijkstra, H; Donleavy, S; Dordei, F; Dorigo, M; Dosil Suárez, A; Dossett, D; Dovbnya, A; Dreimanis, K; Dujany, G; Dupertuis, F; Durante, P; Dzhelyadin, R; Dziurda, A; Dzyuba, A; Easo, S; Egede, U; Egorychev, V; Eidelman, S; Eisenhardt, S; Eitschberger, U; Ekelhof, R; Eklund, L; El Rifai, I; Elsasser, Ch; Ely, S; Esen, S; Evans, H-M; Evans, T; Falabella, A; Färber, C; Farinelli, C; Farley, N; Farry, S; Fay, Rf; Ferguson, D; Fernandez Albor, V; Ferreira Rodrigues, F; Ferro-Luzzi, M; Filippov, S; Fiore, M; Fiorini, M; Firlej, M; Fitzpatrick, C; Fiutowski, T; Fontana, M; Fontanelli, F; Forty, R; Francisco, O; Frank, M; Frei, C; Frosini, M; Fu, J; Furfaro, E; Gallas Torreira, A; Galli, D; Gallorini, S; Gambetta, S; Gandelman, M; Gandini, P; Gao, Y; García Pardiñas, J; Garofoli, J; Garra Tico, J; Garrido, L; Gaspar, C; Gauld, R; Gavardi, L; Gavrilov, G; Geraci, A; Gersabeck, E; Gersabeck, M; Gershon, T; Ghez, Ph; Gianelle, A; Giani', S; Gibson, V; Giubega, L; Gligorov, V V; Göbel, C; Golubkov, D; Golutvin, A; Gomes, A; Gotti, C; Grabalosa Gándara, M; Graciani Diaz, R; Granado Cardoso, L A; Graugés, E; Graziani, G; Grecu, A; Greening, E; Gregson, S; Griffith, P; Grillo, L; Grünberg, O; Gui, B; Gushchin, E; Guz, Yu; Gys, T; Hadjivasiliou, C; Haefeli, G; Haen, C; Haines, S C; Hall, S; Hamilton, B; Hampson, T; Han, X; Hansmann-Menzemer, S; Harnew, N; Harnew, S T; Harrison, J; He, J; Head, T; Heijne, V; Hennessy, K; Henrard, P; Henry, L; Hernando Morata, J A; van Herwijnen, E; Heß, M; Hicheur, A; Hill, D; Hoballah, M; Hombach, C; Hulsbergen, W; Hunt, P; Hussain, N; Hutchcroft, D; Hynds, D; Idzik, M; Ilten, P; Jacobsson, R; Jaeger, A; Jalocha, J; Jans, E; Jaton, P; Jawahery, A; Jing, F; John, M; Johnson, D; Jones, C R; Joram, C; Jost, B; Jurik, N; Kaballo, M; Kandybei, S; Kanso, W; Karacson, M; Karbach, T M; Karodia, S; Kelsey, M; Kenyon, I R; Ketel, T; Khanji, B; Khurewathanakul, C; Klaver, S; Klimaszewski, K; Kochebina, O; Kolpin, M; Komarov, I; Koopman, R F; Koppenburg, P; Korolev, M; Kozlinskiy, A; Kravchuk, L; Kreplin, K; Kreps, M; Krocker, G; Krokovny, P; Kruse, F; Kucewicz, W; Kucharczyk, M; Kudryavtsev, V; Kurek, K; Kvaratskheliya, T; La Thi, V N; Lacarrere, D; Lafferty, G; Lai, A; Lambert, D; Lambert, R W; Lanfranchi, G; Langenbruch, C; Langhans, B; Latham, T; Lazzeroni, C; Le Gac, R; van Leerdam, J; Lees, J-P; Lefèvre, R; Leflat, A; Lefrançois, J; Leo, S; Leroy, O; Lesiak, T; Leverington, B; Li, Y; Likhomanenko, T; Liles, M; Lindner, R; Linn, C; Lionetto, F; Liu, B; Lohn, S; Longstaff, I; Lopes, J H; Lopez-March, N; Lowdon, P; Lu, H; Lucchesi, D; Luo, H; Lupato, A; Luppi, E; Lupton, O; Machefert, F; Machikhiliyan, I V; Maciuc, F; Maev, O; Malde, S; Malinin, A; Manca, G; Mancinelli, G; Maratas, J; Marchand, J F; Marconi, U; Marin Benito, C; Marino, P; Märki, R; Marks, J; Martellotti, G; Martens, A; Martín Sánchez, A; Martinelli, M; Martinez Santos, D; Martinez Vidal, F; Martins Tostes, D; Massafferri, A; Matev, R; Mathe, Z; Matteuzzi, C; Mazurov, A; McCann, M; McCarthy, J; McNab, A; McNulty, R; McSkelly, B; Meadows, B; Meier, F; Meissner, M; Merk, M; Milanes, D A; Minard, M-N; Moggi, N; Molina Rodriguez, J; Monteil, S; Morandin, M; Morawski, P; Mordà, A; Morello, M J; Moron, J; Morris, A-B; Mountain, R; Muheim, F; Müller, K; Mussini, M; Muster, B; Naik, P; Nakada, T; Nandakumar, R; Nasteva, I; Needham, M; Neri, N; Neubert, S; Neufeld, N; Neuner, M; Nguyen, A D; Nguyen, T D; Nguyen-Mau, C; Nicol, M; Niess, V; Niet, R; Nikitin, N; Nikodem, T; Novoselov, A; O'Hanlon, D P; Oblakowska-Mucha, A; Obraztsov, V; Oggero, S; Ogilvy, S; Okhrimenko, O; Oldeman, R; Onderwater, G; Orlandea, M; Otalora Goicochea, J M; Owen, P; Oyanguren, A; Pal, B K; Palano, A; Palombo, F; Palutan, M; Panman, J; Papanestis, A; Pappagallo, M; Pappalardo, L L; Parkes, C; Parkinson, C J; Passaleva, G; Patel, G D; Patel, M; Patrignani, C; Pazos Alvarez, A; Pearce, A; Pellegrino, A; Pepe Altarelli, M; Perazzini, S; Perez Trigo, E; Perret, P; Perrin-Terrin, M; Pescatore, L; Pesen, E; Petridis, K; Petrolini, A; Picatoste Olloqui, E; Pietrzyk, B; Pilař, T; Pinci, D; Pistone, A; Playfer, S; Plo Casasus, M; Polci, F; Poluektov, A; Polycarpo, E; Popov, A; Popov, D; Popovici, B; Potterat, C; Price, E; Prisciandaro, J; Pritchard, A; Prouve, C; Pugatch, V; Puig Navarro, A; Punzi, G; Qian, W; Rachwal, B; Rademacker, J H; Rakotomiaramanana, B; Rama, M; Rangel, M S; Raniuk, I; Rauschmayr, N; Raven, G; Reichert, S; Reid, M M; Dos Reis, A C; Ricciardi, S; Richards, S; Rihl, M; Rinnert, K; Rives Molina, V; Roa Romero, D A; Robbe, P; Rodrigues, A B; Rodrigues, E; Rodriguez Perez, P; Roiser, S; Romanovsky, V; Romero Vidal, A; Rotondo, M; Rouvinet, J; Ruf, T; Ruiz, H; Ruiz Valls, P; Saborido Silva, J J; Sagidova, N; Sail, P; Saitta, B; Salustino Guimaraes, V; Sanchez Mayordomo, C; Sanmartin Sedes, B; Santacesaria, R; Santamarina Rios, C; Santovetti, E; Sarti, A; Satriano, C; Satta, A; Saunders, D M; Savrie, M; Savrina, D; Schiller, M; Schindler, H; Schlupp, M; Schmelling, M; Schmidt, B; Schneider, O; Schopper, A; Schune, M-H; Schwemmer, R; Sciascia, B; Sciubba, A; Seco, M; Semennikov, A; Sepp, I; Serra, N; Serrano, J; Sestini, L; Seyfert, P; Shapkin, M; Shapoval, I; Shcheglov, Y; Shears, T; Shekhtman, L; Shevchenko, V; Shires, A; Silva Coutinho, R; Simi, G; Sirendi, M; Skidmore, N; Skwarnicki, T; Smith, N A; Smith, E; Smith, E; Smith, J; Smith, M; Snoek, H; Sokoloff, M D; Soler, F J P; Soomro, F; Souza, D; Souza De Paula, B; Spaan, B; Sparkes, A; Spradlin, P; Sridharan, S; Stagni, F; Stahl, M; Stahl, S; Steinkamp, O; Stenyakin, O; Stevenson, S; Stoica, S; Stone, S; Storaci, B; Stracka, S; Straticiuc, M; Straumann, U; Stroili, R; Subbiah, V K; Sun, L; Sutcliffe, W; Swientek, K; Swientek, S; Syropoulos, V; Szczekowski, M; Szczypka, P; Szilard, D; Szumlak, T; T'Jampens, S; Teklishyn, M; Tellarini, G; Teubert, F; Thomas, C; Thomas, E; van Tilburg, J; Tisserand, V; Tobin, M; Tolk, S; Tomassetti, L; Tonelli, D; Topp-Joergensen, S; Torr, N; Tournefier, E; Tourneur, S; Tran, M T; Tresch, M; Tsaregorodtsev, A; Tsopelas, P; Tuning, N; Ubeda Garcia, M; Ukleja, A; Ustyuzhanin, A; Uwer, U; Vagnoni, V; Valenti, G; Vallier, A; Vazquez Gomez, R; Vazquez Regueiro, P; Vázquez Sierra, C; Vecchi, S; Velthuis, J J; Veltri, M; Veneziano, G; Vesterinen, M; Viaud, B; Vieira, D; Vieites Diaz, M; Vilasis-Cardona, X; Vollhardt, A; Volyanskyy, D; Voong, D; Vorobyev, A; Vorobyev, V; Voß, C; Voss, H; de Vries, J A; Waldi, R; Wallace, C; Wallace, R; Walsh, J; Wandernoth, S; Wang, J; Ward, D R; Watson, N K; Websdale, D; Whitehead, M; Wicht, J; Wiedner, D; Wilkinson, G; Williams, M P; Williams, M; Wilson, F F; Wimberley, J; Wishahi, J; Wislicki, W; Witek, M; Wormser, G; Wotton, S A; Wright, S; Wu, S; Wyllie, K; Xie, Y; Xing, Z; Xu, Z; Yang, Z; Yuan, X; Yushchenko, O; Zangoli, M; Zavertyaev, M; Zhang, L; Zhang, W C; Zhang, Y; Zhelezov, A; Zhokhov, A; Zhong, L; Zvyagin, A

2014-10-10

A baryonic decay of the B(c)(+) meson, B(c)(+) → J/ψppπ(+), is observed for the first time, with a significance of 7.3 standard deviations, in pp collision data collected with the LHCb detector and corresponding to an integrated luminosity of 3.0 fb(-1) taken at center-of-mass energies of 7 and 8 TeV. With the B(c)(+) → J/ψπ(+) decay as the normalization channel, the ratio of branching fractions is measured to be B(B(c)(+) → J/ψppπ(+))/B(B(c)(+) → J/ψπ(+)) = 0.143(-0.034)(+0.039)(stat) ± 0.013(syst). The mass of the B(c)(+) meson is determined as M(B(c)(+) = 6274.0 ± 1.8(stat) ± 0.4(syst) MeV/c(2), using the B(c)(+) → J/ψppπ(+) channel.

Harpin-induced expression and transgenic overexpression of the phloem protein gene AtPP2-A1 in Arabidopsis repress phloem feeding of the green peach aphid Myzus persicae

PubMed Central

2011-01-01

Background Treatment of plants with HrpNEa, a protein of harpin group produced by Gram-negative plant pathogenic bacteria, induces plant resistance to insect herbivores, including the green peach aphid Myzus persicae, a generalist phloem-feeding insect. Under attacks by phloem-feeding insects, plants defend themselves using the phloem-based defense mechanism, which is supposed to involve the phloem protein 2 (PP2), one of the most abundant proteins in the phloem sap. The purpose of this study was to obtain genetic evidence for the function of the Arabidopsis thaliana (Arabidopsis) PP2-encoding gene AtPP2-A1 in resistance to M. persicae when the plant was treated with HrpNEa and after the plant was transformed with AtPP2-A1. Results The electrical penetration graph technique was used to visualize the phloem-feeding activities of apterous agamic M. persicae females on leaves of Arabidopsis plants treated with HrpNEa and an inactive protein control, respectively. A repression of phloem feeding was induced by HrpNEa in wild-type (WT) Arabidopsis but not in atpp2-a1/E/142, the plant mutant that had a defect in the AtPP2-A1 gene, the most HrpNEa-responsive of 30 AtPP2 genes. In WT rather than atpp2-a1/E/142, the deterrent effect of HrpNEa treatment on the phloem-feeding activity accompanied an enhancement of AtPP2-A1 expression. In PP2OETAt (AtPP2-A1-overexpression transgenic Arabidopsis thaliana) plants, abundant amounts of the AtPP2-A1 gene transcript were detected in different organs, including leaves, stems, calyces, and petals. All these organs had a deterrent effect on the phloem-feeding activity compared with the same organs of the transgenic control plant. When a large-scale aphid population was monitored for 24 hours, there was a significant decrease in the number of aphids that colonized leaves of HrpNEa-treated WT and PP2OETAt plants, respectively, compared with control plants. Conclusions The repression in phloem-feeding activities of M. persicae as a result of AtPP2-A1 overexpression, and as a deterrent effect of HrpNEa treatment in WT Arabidopsis rather than the atpp2-a1/E/142 mutant suggest that AtPP2-A1 plays a role in plant resistance to the insect, particularly at the phloem-feeding stage. The accompanied change of aphid population in leaf colonies suggests that the function of AtPP2-A1 is related to colonization of the plant. PMID:21226963

Harpin-induced expression and transgenic overexpression of the phloem protein gene AtPP2-A1 in Arabidopsis repress phloem feeding of the green peach aphid Myzus persicae.

PubMed

Zhang, Chunling; Shi, Haojie; Chen, Lei; Wang, Xiaomeng; Lü, Beibei; Zhang, Shuping; Liang, Yuan; Liu, Ruoxue; Qian, Jun; Sun, Weiwei; You, Zhenzhen; Dong, Hansong

2011-01-13

Treatment of plants with HrpNEa, a protein of harpin group produced by Gram-negative plant pathogenic bacteria, induces plant resistance to insect herbivores, including the green peach aphid Myzus persicae, a generalist phloem-feeding insect. Under attacks by phloem-feeding insects, plants defend themselves using the phloem-based defense mechanism, which is supposed to involve the phloem protein 2 (PP2), one of the most abundant proteins in the phloem sap. The purpose of this study was to obtain genetic evidence for the function of the Arabidopsis thaliana (Arabidopsis) PP2-encoding gene AtPP2-A1 in resistance to M. persicae when the plant was treated with HrpNEa and after the plant was transformed with AtPP2-A1. The electrical penetration graph technique was used to visualize the phloem-feeding activities of apterous agamic M. persicae females on leaves of Arabidopsis plants treated with HrpNEa and an inactive protein control, respectively. A repression of phloem feeding was induced by HrpNEa in wild-type (WT) Arabidopsis but not in atpp2-a1/E/142, the plant mutant that had a defect in the AtPP2-A1 gene, the most HrpNEa-responsive of 30 AtPP2 genes. In WT rather than atpp2-a1/E/142, the deterrent effect of HrpNEa treatment on the phloem-feeding activity accompanied an enhancement of AtPP2-A1 expression. In PP2OETAt (AtPP2-A1-overexpression transgenic Arabidopsis thaliana) plants, abundant amounts of the AtPP2-A1 gene transcript were detected in different organs, including leaves, stems, calyces, and petals. All these organs had a deterrent effect on the phloem-feeding activity compared with the same organs of the transgenic control plant. When a large-scale aphid population was monitored for 24 hours, there was a significant decrease in the number of aphids that colonized leaves of HrpNEa-treated WT and PP2OETAt plants, respectively, compared with control plants. The repression in phloem-feeding activities of M. persicae as a result of AtPP2-A1 overexpression, and as a deterrent effect of HrpNEa treatment in WT Arabidopsis rather than the atpp2-a1/E/142 mutant suggest that AtPP2-A1 plays a role in plant resistance to the insect, particularly at the phloem-feeding stage. The accompanied change of aphid population in leaf colonies suggests that the function of AtPP2-A1 is related to colonization of the plant.

Enhanced ethylene responsiveness in the Arabidopsis eer1 mutant results from a loss-of-function mutation in the protein phosphatase 2A A regulatory subunit, RCN1.

PubMed

Larsen, Paul Brian; Cancel, Jesse Daniel

2003-06-01

Ethylene signaling in Arabidopsis begins with a family of five ethylene receptors that regulate the activity of the Raf-like kinase, CTR1. Recent work to identify novel factors required for modulating ethylene signaling resulted in the isolation of enhanced ethylene response 1 (eer1), a mutant that displays both increased sensitivity and increased amplitude of response to ethylene. Molecular cloning of eer1 reveals that its mutant phenotype results from a loss-of-function mutation in the previously characterized RCN1, one of three PP2A A regulatory subunits in Arabidopsis. Our analysis shows that neither RCN1 expression nor PP2A activity is regulated by ethylene. Instead, we found that Arabidopsis PP2A-1C, a PP2A catalytic subunit previously characterized as interacting with RCN1, associates strongly with the kinase domain of CTR1 in vitro. This likely represents a role for PP2A in modulation of CTR1 activity because an in vitro kinase assay did not reveal phosphorylation of either RCN1 or PP2A-1C by CTR1, indicating that neither of them is a substrate for CTR1. PP2A activity is required for Ras-dependent activation of mammalian Raf, with reductions in PP2A activity significantly compromising the effectiveness of this mechanism. Our genetic and biochemical results suggest that a similar requirement for PP2A activity exists for ethylene signaling, with loss-of-function mutations affecting PP2A activity possibly reducing the effectiveness of CTR1 activation, thus lowering the threshold required for manifestation of ethylene response.

MCLR-induced PP2A inhibition and subsequent Rac1 inactivation and hyperphosphorylation of cytoskeleton-associated proteins are involved in cytoskeleton rearrangement in SMMC-7721 human liver cancer cell line.

PubMed

Wang, Hao; Liu, Jinghui; Lin, Shuyan; Wang, Beilei; Xing, Mingluan; Guo, Zonglou; Xu, Lihong

2014-10-01

Cyanobacteria-derived toxin microcystin-LR (MCLR) has been widely investigated in its effects on normal cells, there is little information concerning its effects on cancer cells. In the present study, the SMMC-7721 human liver cancer cell line treated with MCLR was used to investigate the change of PP2A, cytoskeleton rearrangement, phosphorylation levels of PP2A substrates that related with cytoskeleton stability and explored underlying mechanisms. Here, we confirmed that MCLR entered into SMMC-7721 cells, bound to PP2A/C subunit and inhibited the activity of PP2A. The upregulation of phosphorylation of the PP2A/C subunit and PP2A regulation protein α4, as well as the change in the association of PP2A/C with α4, were responsible for the decrease in PP2A activity. Another novel finding is that the rearrangement of filamentous actin and microtubules led by MCLR may attribute to the increased phosphorylation of HSP27, VASP and cofilin due to PP2A inhibition. As a result of weakened interactions with PP2A and alterations in its subcellular localization, Rac1 may contribute to the cytoskeletal rearrangement induced by MCLR in SMMC-7721 cells. The current paper presents the first report demonstrating the characteristic of PP2A in MCLR exposed cancer cells, which were more susceptible to MCLR compared with the normal cell lines we previously found, which may be owing to the absence of some type of compensatory mechanisms. The hyperphosphorylation of cytoskeleton-associated proteins and Rac1 inactivation which were induced by inhibition of PP2A are shown to be involved in cytoskeleton rearrangement. Copyright © 2014 Elsevier Ltd. All rights reserved.

Conserved regulatory mechanism controls the development of cells with rooting functions in land plants.

PubMed

Tam, Thomas Ho Yuen; Catarino, Bruno; Dolan, Liam

2015-07-21

Land plants develop filamentous cells-root hairs, rhizoids, and caulonemata-at the interface with the soil. Members of the group XI basic helix-loop-helix (bHLH) transcription factors encoded by LOTUS JAPONICUS ROOTHAIRLESS1-LIKE (LRL) genes positively regulate the development of root hairs in the angiosperms Lotus japonicus, Arabidopsis thaliana, and rice (Oryza sativa). Here we show that auxin promotes rhizoid and caulonema development by positively regulating the expression of PpLRL1 and PpLRL2, the two LRL genes in the Physcomitrella patens genome. Although the group VIII bHLH proteins, AtROOT HAIR DEFECTIVE6 and AtROOT HAIR DEFECTIVE SIX-LIKE1, promote root-hair development by positively regulating the expression of AtLRL3 in A. thaliana, LRL genes promote rhizoid development independently of PpROOT HAIR DEFECTIVE SIX-LIKE1 and PpROOT HAIR DEFECITVE SIX-LIKE2 (PpRSL1 and PpRSL2) gene function in P. patens. Together, these data demonstrate that both LRL and RSL genes are components of an ancient auxin-regulated gene network that controls the development of tip-growing cells with rooting functions among most extant land plants. Although this network has diverged in the moss and the angiosperm lineages, our data demonstrate that the core network acted in the last common ancestor of the mosses and angiosperms that existed sometime before 420 million years ago.

Conserved regulatory mechanism controls the development of cells with rooting functions in land plants

PubMed Central

Tam, Thomas Ho Yuen; Catarino, Bruno; Dolan, Liam

2015-01-01

Land plants develop filamentous cells—root hairs, rhizoids, and caulonemata—at the interface with the soil. Members of the group XI basic helix–loop–helix (bHLH) transcription factors encoded by LOTUS JAPONICUS ROOTHAIRLESS1-LIKE (LRL) genes positively regulate the development of root hairs in the angiosperms Lotus japonicus, Arabidopsis thaliana, and rice (Oryza sativa). Here we show that auxin promotes rhizoid and caulonema development by positively regulating the expression of PpLRL1 and PpLRL2, the two LRL genes in the Physcomitrella patens genome. Although the group VIII bHLH proteins, AtROOT HAIR DEFECTIVE6 and AtROOT HAIR DEFECTIVE SIX-LIKE1, promote root-hair development by positively regulating the expression of AtLRL3 in A. thaliana, LRL genes promote rhizoid development independently of PpROOT HAIR DEFECTIVE SIX-LIKE1 and PpROOT HAIR DEFECITVE SIX-LIKE2 (PpRSL1 and PpRSL2) gene function in P. patens. Together, these data demonstrate that both LRL and RSL genes are components of an ancient auxin-regulated gene network that controls the development of tip-growing cells with rooting functions among most extant land plants. Although this network has diverged in the moss and the angiosperm lineages, our data demonstrate that the core network acted in the last common ancestor of the mosses and angiosperms that existed sometime before 420 million years ago. PMID:26150509

The B55α Regulatory Subunit of Protein Phosphatase 2A Mediates Fibroblast Growth Factor-Induced p107 Dephosphorylation and Growth Arrest in Chondrocytes

PubMed Central

Daempfling, Lea

2013-01-01

Fibroblast growth factor (FGF)-induced growth arrest of chondrocytes is a unique cell type-specific response which contrasts with the proliferative response of most cell types and underlies several genetic skeletal disorders caused by activating FGF receptor (FGFR) mutations. We have shown that one of the earliest key events in FGF-induced growth arrest is dephosphorylation of the retinoblastoma protein (Rb) family member p107 by protein phosphatase 2A (PP2A), a ubiquitously expressed multisubunit phosphatase. In this report, we show that the PP2A-B55α holoenzyme (PP2A containing the B55α subunit) is responsible for this phenomenon. Only the B55α (55-kDa regulatory subunit, alpha isoform) regulatory subunit of PP2A was able to bind p107, and this interaction was induced by FGF in chondrocytes but not in other cell types. Small interfering RNA (siRNA)-mediated knockdown of B55α prevented p107 dephosphorylation and FGF-induced growth arrest of RCS (rat chondrosarcoma) chondrocytes. Importantly, the B55α subunit bound with higher affinity to dephosphorylated p107. Since the p107 region interacting with B55α is also the site of cyclin-dependent kinase (CDK) binding, B55α association may also prevent p107 phosphorylation by CDKs. FGF treatment induces dephosphorylation of the B55α subunit itself on several serine residues that drastically increases the affinity of B55α for the PP2A A/C dimer and p107. Together these observations suggest a novel mechanism of p107 dephosphorylation mediated by activation of PP2A through B55α dephosphorylation. This mechanism might be a general signal transduction pathway used by PP2A to initiate cell cycle arrest when required by external signals. PMID:23716589

Identification of Peach NAP Transcription Factor Genes and Characterization of their Expression in Vegetative and Reproductive Organs during Development and Senescence

PubMed Central

Li, Fang; Li, Jinjin; Qian, Ming; Han, Mingyu; Cao, Lijun; Liu, Hangkong; Zhang, Dong; Zhao, Caiping

2016-01-01

The NAP (NAC-like, activated by AP3/P1) transcription factor belongs to a subfamily of the NAC transcription factor family, and is believed to have an important role in regulating plant growth and development. However, there is very little information about this subfamily in Rosaceous plants. We identified seven NAP genes in the peach genome. PpNAP2 was categorized in the NAP I group, and contained a conserved transcription activation region. The other PpNAP genes belonged to the NAP II group. The expression patterns of the PpNAP genes differed in various organs and developmental stages. PpNAP1 and PpNAP2 were highly expressed in mature and senescing flowers, but not in leaves, fruits, and flower buds. PpNAP3 and PpNAP5 were only expressed in leaves. The PpNAP4 expression level was high in mature and senescing fruits, while PpNAP6 and PpNAP7 expression was up-regulated in mature and senescent leaves and flowers. During the fruit development period, the PpNAP4 and PpNAP6 expression levels rapidly increased during the S1 and S4 stages, which suggests these genes are involved in the first exponential growth phase and fruit ripening. During the fruit ripening and softening period, the PpNAP1, PpNAP4, and PpNAP6 expression levels were high during the early storage period, which was accompanied by a rapid increase in ethylene production. PpNAP1, PpNAP4, and PpNAP6 expression slowly increased during the middle or late storage periods, and peaked at the end of the storage period. Additionally, abscisic acid (ABA)-treated fruits were softer and produced more ethylene than the controls. Furthermore, the PpNAP1, PpNAP4, and PpNAP6 expression levels were higher in ABA-treated fruits. These results suggest that PpNAP1, PpNAP4, and PpNAP6 are responsive to ABA and may regulate peach fruit ripening. PMID:26909092

PP2A-B56 opposes Mps1 phosphorylation of Knl1 and thereby promotes spindle assembly checkpoint silencing.

PubMed

Espert, Antonio; Uluocak, Pelin; Bastos, Ricardo Nunes; Mangat, Davinderpreet; Graab, Philipp; Gruneberg, Ulrike

2014-09-29

The spindle assembly checkpoint (SAC) monitors correct attachment of chromosomes to microtubules, an important safeguard mechanism ensuring faithful chromosome segregation in eukaryotic cells. How the SAC signal is turned off once all the chromosomes have successfully attached to the spindle remains an unresolved question. Mps1 phosphorylation of Knl1 results in recruitment of the SAC proteins Bub1, Bub3, and BubR1 to the kinetochore and production of the wait-anaphase signal. SAC silencing is therefore expected to involve a phosphatase opposing Mps1. Here we demonstrate in vivo and in vitro that BubR1-associated PP2A-B56 is a key phosphatase for the removal of the Mps1-mediated Knl1 phosphorylations necessary for Bub1/BubR1 recruitment in mammalian cells. SAC silencing is thus promoted by a negative feedback loop involving the Mps1-dependent recruitment of a phosphatase opposing Mps1. Our findings extend the previously reported role for BubR1-associated PP2A-B56 in opposing Aurora B and suggest that BubR1-bound PP2A-B56 integrates kinetochore surveillance and silencing of the SAC. © 2014 Espert et al.

A New Protein Phosphatase 2C (FsPP2C1) Induced by Abscisic Acid Is Specifically Expressed in Dormant Beechnut Seeds1

PubMed Central

Lorenzo, Oscar; Rodríguez, Dolores; Nicolás, Gregorio; Rodríguez, Pedro L.; Nicolás, Carlos

2001-01-01

An abscisic acid (ABA)-induced cDNA fragment encoding a putative protein phosphatase 2C (PP2C) was obtained by means of differential reverse transcriptase-polymerase chain reaction approach. The full-length clone was isolated from a cDNA library constructed using mRNA from ABA-treated beechnut (Fagus sylvatica) seeds. This clone presents all the features of plant type PP2C and exhibits homology to members of this family such as AthPP2CA (61%), ABI1 (48%), or ABI2 (47%), therefore it was named FsPP2C1. The expression of FsPP2C1 is detected in dormant seeds and increases after ABA treatment, when seeds are maintained dormant, but it decreases and tends to disappear when dormancy is being released by stratification or under gibberellic acid treatment. Moreover, drought stress seems to have no effect on FsPP2C1 transcript accumulation. The FsPP2C1 transcript expression is tissue specific and was found to accumulate in ABA-treated seeds rather than in other ABA-treated vegetative tissues examined. These results suggest that the corresponding protein could be related to ABA-induced seed dormancy. By expressing FsPP2C1 in Escherichia coli as a histidine tag fusion protein, we have obtained direct biochemical evidence supporting Mg2+-dependent phosphatase activity of this protein. PMID:11299374

Penetration of Face Hardened Bullet Proof Steel by Yawed .50 cal. AP (armor Piercing) Bullets at O deg. Obliquity

DTIC Science & Technology

1943-07-09

for sevarad platos a o"’l i~u.Li * DAVID I. 157"iCYI, Copy, tos 81*,AI’C Doa ’* (dir*et) B3uiad Deec !’Alb (diroot) Lt, Gseauque 10 tJt. Jolmson- E...2233 10 CP N1 1/21’ Hole. 42 2265 55 PP NH 2" Pin S. 43 2260 53 PP NH 3" x 4" Crack. 44 2240 25 PP RJ HB No Crack. 45 2252 27 PP RJ RB No Cracks, 46

A novel protein phosphatase 2A (PP2A) is involved in the transformation of human protozoan parasite Trypanosoma cruzi.

PubMed Central

González, Jorge; Cornejo, Alberto; Santos, Marcia R M; Cordero, Esteban M; Gutiérrez, Bessy; Porcile, Patricio; Mortara, Renato A; Sagua, Hernán; Da Silveira, José Franco; Araya, Jorge E

2003-01-01

Here we provide evidence for a critical role of PP2As (protein phosphatase 2As) in the transformation of Trypanosoma cruzi. In axenic medium at pH 5.0, trypomastigotes rapidly transform into amastigotes, a process blocked by okadaic acid, a potent PP2A inhibitor, at concentrations as low as 0.1 microM. 1-Norokadaone, an inactive okadaic acid analogue, did not affect the transformation. Electron microscopy studies indicated that okadaic acid-treated trypomastigotes had not undergone ultrastructural modifications, reinforcing the idea that PP2A inhibits transformation. Using a microcystin-Sepharose affinity column we purified the native T. cruzi PP2A. The enzyme displayed activity against 32P-labelled phosphorylase a that was inhibited in a dose-dependent manner by okadaic acid. The protein was also submitted to MS and, from the peptides obtained, degenerate primers were used to clone a novel T. cruzi PP2A enzyme by PCR. The isolated gene encodes a protein of 303 amino acids, termed TcPP2A, which displayed a high degree of homology (86%) with the catalytic subunit of Trypanosoma brucei PP2A. Northern-blot analysis revealed the presence of a major 2.1-kb mRNA hybridizing in all T. cruzi developmental stages. Southern-blot analysis suggested that the TcPP2A gene is present in low copy number in the T. cruzi genome. These results are consistent with the mapping of PP2A genes in two chromosomal bands by pulsed-field gel electrophoresis and chromoblot hybridization. Our studies suggest that in T. cruzi PP2A is important for the complete transformation of trypomastigotes into amastigotes during the life cycle of this protozoan parasite. PMID:12737627

Control of Aspergillus growth and aflatoxin production using antioxidants at different conditions of water activity and pH.

PubMed

Nesci, A; Rodriguez, M; Etcheverry, M

2003-01-01

The effect of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), trihydroxybutyrophenone (THB) and propyl paraben (PP) (at concentrations of 1, 10 and 20 mmol l(-1)) on germination, growth and aflatoxin B1 production by Aspergillus section Flavi was evaluated. Studies on the percentage of spore germination, elongation rate, growth rate and aflatoxin B1 production were carried out in vitro in relation to water activity (aw) at 0.982, 0.937, 0.809 and 0.747 values. At 0.809 and 0.747aw values none of the isolates was able to germinate. Overall, PP and BHA were the antioxidants most effective at inhibiting germination of both species. In the presence of the lowest concentration of BHA and PP (1 mmol l(-1)) the conidial germination percentage ranged from 2 to 19% after 15 h of incubation at the highest water activity tested. BHA and PP at 10-20 mmol l(-1) completely inhibited conidial germination. The antioxidants more efficient in controlling Aspergillus elongation rate were PP, BHT and BHA. All strains were much more sensitive to all antioxidants tested on the percentage of spore germination and growth rate at 0.937aw. The antioxidants PP and BHA completely inhibited aflatoxin B1 production by all strains when added at 1 mmol l(-1). Decreased aflatoxin B1 levels in comparison with the control, were observed with BHT at 1, 10 and 20 mmol(-1) with the strain T20 at 0.982aw. In contrast, stimulation was observed with the antioxidant THB at 10 and 20 mmol l(-1) at 0.937aw with the strains T20 and T23. The effect of BHA and PP at 1 mmol l(-1) on lag phase and growth rate was maintained in the pH range between 6 and 8. At all pH values the inhibitory effect of BHA was higher than PP. No aflatoxin B1 was detected at all pH values. The data show that BHA and PP could be considered as effective fungitoxicants for A. flavus and A. parasiticus. The information obtained show promise for controlling growth and aflatoxin B1 in stored maize. Futher studies should be carried out to examine the potential for antioxidants, such as BHA and PP to effectively control both growth and aflatoxin production.

The Aurora kinase Ipl1 maintains the centromeric localization of PP2A to protect cohesin during meiosis.

PubMed

Yu, Hong-Guo; Koshland, Douglas

2007-03-26

Homologue segregation during the first meiotic division requires the proper spatial regulation of sister chromatid cohesion and its dissolution along chromosome arms, but its protection at centromeric regions. This protection requires the conserved MEI-S332/Sgo1 proteins that localize to centromeric regions and also recruit the PP2A phosphatase by binding its regulatory subunit, Rts1. Centromeric Rts1/PP2A then locally prevents cohesion dissolution possibly by dephosphorylating the protein complex cohesin. We show that Aurora B kinase in Saccharomyces cerevisiae (Ipl1) is also essential for the protection of meiotic centromeric cohesion. Coupled with a previous study in Drosophila melanogaster, this meiotic function of Aurora B kinase appears to be conserved among eukaryotes. Furthermore, we show that Sgo1 recruits Ipl1 to centromeric regions. In the absence of Ipl1, Rts1 can initially bind to centromeric regions but disappears from these regions after anaphase I onset. We suggest that centromeric Ipl1 ensures the continued centromeric presence of active Rts1/PP2A, which in turn locally protects cohesin and cohesion.

Night sleep electroencephalogram power spectral analysis in excessive daytime sleepiness disorders.

PubMed

Reimão, R

1991-06-01

A group of 53 patients (40 males, 13 females) with mean age of 49 years, ranging from 30 to 70 years, was evaluated in the following excessive daytime sleepiness (EDS) disorders: obstructive sleep apnea syndrome (B4a), periodic movements in sleep (B5a), affective disorder (B2a), functional psychiatric non affective disorder (B2b). We considered all adult patients referred to the Center sequentially with no other distinctions but these three criteria: (a) EDS was the main complaint; (b) right handed; (c) not using psychotropic drugs for two weeks prior to the all-night polysomnography. EEG (C3/A1, C4/A2) samples from 2 to 10 minutes of each stage of the first REM cycle were chosen. The data was recorded simultaneously in magnetic tape and then fed into a computer for power spectral analysis. The percentage of power (PP) in each band calculated in relation to the total EEG power was determined of subsequent sections of 20.4 s for the following frequency bands: delta, theta, alpha and beta. The PP in all EDS patients sample had a tendency to decrease progressively from the slowest to the fastest frequency bands, in every sleep stage. PP distribution in the delta range increased progressively from stage 1 to stage 4; stage REM levels were close to stage 2 levels. In an EDS patients interhemispheric coherence was high in every band and sleep stage. B4a patients sample PP had a tendency to decrease progressively from the slowest to the fastest frequency bands, in every sleep stage; PP distribution in the delta range increased progressively from stage 1 to stage 4; stage REM levels were between stage 1 and stage 2 levels.(ABSTRACT TRUNCATED AT 250 WORDS)

A novel function of twins, B subunit of protein phosphatase 2A, in regulating actin polymerization.

PubMed

Yeh, Po-An; Chang, Ching-Jin

2017-01-01

Actin is an important component of the cytoskeleton and its polymerization is delicately regulated by several kinases and phosphatases. Heterotrimeric protein phosphatase 2A (PP2A) is a potent phosphatase that is crucial for cell proliferation, apoptosis, tumorigenesis, signal transduction, cytoskeleton arrangement, and neurodegeneration. To facilitate these varied functions, different regulators determine the different targets of PP2A. Among these regulators of PP2A, the B subunits in particular may be involved in cytoskeleton arrangement. However, little is known about the role of PP2A in actin polymerization in vivo. Using sophisticated fly genetics, we demonstrated a novel function for the fly B subunit, twins, to promote actin polymerization in varied tissue types, suggesting a broad and conserved effect. Furthermore, our genetic data suggest that twins may act upstream of the actin-polymerized-proteins, Moesin and Myosin-light-chain, and downstream of Rho to promote actin polymerization. This work opens a new avenue for exploring the biological functions of a PP2A regulator, twins, in cytoskeleton regulation.

A novel function of twins, B subunit of protein phosphatase 2A, in regulating actin polymerization

PubMed Central

Chang, Ching-Jin

2017-01-01

Actin is an important component of the cytoskeleton and its polymerization is delicately regulated by several kinases and phosphatases. Heterotrimeric protein phosphatase 2A (PP2A) is a potent phosphatase that is crucial for cell proliferation, apoptosis, tumorigenesis, signal transduction, cytoskeleton arrangement, and neurodegeneration. To facilitate these varied functions, different regulators determine the different targets of PP2A. Among these regulators of PP2A, the B subunits in particular may be involved in cytoskeleton arrangement. However, little is known about the role of PP2A in actin polymerization in vivo. Using sophisticated fly genetics, we demonstrated a novel function for the fly B subunit, twins, to promote actin polymerization in varied tissue types, suggesting a broad and conserved effect. Furthermore, our genetic data suggest that twins may act upstream of the actin-polymerized-proteins, Moesin and Myosin-light-chain, and downstream of Rho to promote actin polymerization. This work opens a new avenue for exploring the biological functions of a PP2A regulator, twins, in cytoskeleton regulation. PMID:28977036

Anti-proliferation of triple-negative breast cancer cells with physagulide P: ROS/JNK signaling pathway induces apoptosis and autophagic cell death

PubMed Central

Gao, Cai-Yun; Ma, Ting; Zhang, Hao; Zhou, Miao-Miao; Yang, Yan-Wei; Yang, Lei; Kong, Ling-Yi

2017-01-01

Physagulide P (PP), a new natural compound, was isolated from Physalis angulate L. in our laboratory. In this study, we demonstrated that PP potently suppressed cell proliferation by inducing G2/M phase arrest in MDA-MB-231 and MDA-MB-468 cells. Moreover, PP provoked apoptosis by decreasing the mitochondrial membrane potential and elevating the Bax/Bcl-2 protein expression ratio. The caspase inhibitor Z-VAD-FMK partly restore cell viability, suggesting that apoptosis plays as an important role in the anti-proliferative effect of PP. PP-treated cells also underwent autophagy, as evidenced by the formation of autophagosomes and the accumulation of LC3BII. Furthermore, the knockdown of LC3B reduced PP-induced cytotoxicity, indicating that autophagy played an anticancer effect. PP also induced the generation of reactive oxygen species (ROS) and resulted in c-Jun N-terminal kinases (JNK) activation. Accordingly, JNK siRNA significantly attenuated PP-triggered apoptosis and autophagy, and ROS scavengers almost completely reverse this apoptosis and autophagy. The ROS scavenger also blocked PP-induced G2/M phase arrest and the phosphorylation of JNK. Our results revealed that PP induced G2/M phase arrest, apoptosis and autophagy via the ROS/JNK signaling pathway in MDA-MB-231 and MDA-MB-468 cells. Therefore, PP is a promising candidate for the development of antitumor drugs for the treatment of triple-negative breast cancer. PMID:28969050

Regulation of protein phosphatase 2A during embryonic diapause process in the silkworm, Bombyx mori.

PubMed

Gu, Shi-Hong; Hsieh, Hsiao-Yen; Lin, Pei-Ling

2017-11-01

Regulation of protein phosphorylation requires coordinated interactions between protein kinases and protein phosphatases. In the present study, we investigated regulation of protein phosphatase 2A (PP2A) during the embryonic diapause process of B. mori. An immunoblotting analysis showed that Bombyx eggs contained a catalytic C subunit, a major regulatory B subunit (B55/PR55 subunit), and a structural A subunit, with the A and B subunits undergoing differential changes between diapause and non-diapause eggs during embryonic process. In non-diapause eggs, eggs whose diapause initiation was prevented by HCl, and eggs in which diapause had been terminated by chilling of diapausing eggs at 5°C for 70days and then were transferred to 25°C, protein levels of the A and B subunits of PP2A gradually increased toward embryonic development. However, protein levels of the A and B subunits in diapause eggs remained at low levels during the first 8days after oviposition. The direct determination of PP2A enzymatic activity showed that the activity remained at low levels in diapause eggs during the first 8days after oviposition. However, in non-diapause eggs, eggs whose diapause initiation was prevented by HCl, and eggs in which diapause had been terminated by chilling, PP2A enzymatic activity sharply increased during the first several days, reached a peak during the middle embryonic development, and then greatly decreased 3 or 4days before hatching. Examination of temporal changes in mRNA expression levels of the catalytic β subunit and regulatory subunit of PP2A showed high levels in eggs whose diapause initiation was prevented by HCl compared to those in diapause eggs. These results demonstrate that the higher PP2A gene expression and PP2A A and B subunit protein levels and increased enzymatic activity are related to embryonic development of B. mori. Copyright © 2017 Elsevier Ltd. All rights reserved.

Aircraft Hydraulic Systems Dynamic Analysis

DTIC Science & Technology

1978-10-01

002O,30 DAoo DPV AtH Tapf1AR91 15017VLOL6l 2O 30117l t1 l .43# 1 S 11 C OATA--~8 T 0 PACT~?/PP TL/t 9PIIT b l’ I 0 AL91* E?’S/2 v T~f 1 U-M. 322 ...PRESSURE SLOT DO 160 toloWsl~pp 1P(IýPESPAtT,4 PSS) GO TO 162 OLEAX*(. ZESP -LPRFSS)*PLEAX*DT GO TO 164~ 16? L KUESL~S SPKD 164tqUFrRS!;-;4! ? L PP E

The anti-esophageal cancer cell activity by a novel tyrosine/phosphoinositide kinase inhibitor PP121

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peng, Yi; Zhou, Yajuan; Department of Radiation Oncology, Hubei Cancer Hospital, Wuhan 430071

Here we explored the potential effect of PP121, a novel dual inhibitor of tyrosine and phosphoinositide kinases, against human esophageal cancer cells. We showed that PP121 exerted potent cytotoxic effect in primary (patient-derived) and established (Eca-109, TE-1 and TE-3 lines) esophageal cancer cells, possibly through activating caspase-3-dependnent apoptosis. PP121 was, however, non-cytotoxic to the normal human esophageal epithelial cells (EECs). At the molecular level, we showed that PP121 blocked Akt-mTOR (mammalian target of rapamycin) activation in esophageal cancer cells, which was restored by introducing a constitutively-active Akt (CA-Akt). Yet, CA-Akt only partly inhibited cytotoxicity by PP121 in Eca-109 cells. Importantly, wemore » showed that PP121 inhibited nuclear factor kappa B (NFκB) signaling activation in esophageal cancer cells, which appeared independent of Akt-mTOR blockage. In vivo, oral administration of PP121 remarkably inhibited Eca-109 xenograft growth in nude mice, and significantly improved mice survival. Further, the immunohistochemistry (IHC) and Western blot assays analyzing xenografted tumors showed that PP121 inhibited Akt-mTOR and NFκB activations in vivo. Together, we demonstrate that PP121 potently inhibits esophageal cancer cells in vitro and in vivo, possibly through concurrently inhibiting Akt-mTOR and NFκB signalings. - Highlights: • PP121 is cytotoxic against primary and established esophageal cancer cells. • PP121 induces caspase-3-dependnent apoptosis in esophageal cancer cells. • PP121 blocks Akt-mTOR activation in esophageal cancer cells. • PP121 inhibits NFκB activation, independent of Akt-mTOR blockage. • PP121 inhibits Eca-109 xenograft growth and Akt-mTOR/NFκB activation in vivo.« less

Sperm motility development in the epididymis is associated with decreased glycogen synthase kinase-3 and protein phosphatase 1 activity.

PubMed

Vijayaraghavan, S; Stephens, D T; Trautman, K; Smith, G D; Khatra, B; da Cruz e Silva, E F; Greengard, P

1996-03-01

Immotile bovine caput epididymal sperm contain levels of protein phosphatase activity twofold higher than do mature motile caudal sperm. Comparison of the inhibition profiles of endogenous phosphatase activities detected by okadaic acid (OA) and calyculin A (CA) revealed a pattern consistent with the predominance of a type 1 protein phosphatase (PP1). Immunoblot analysis identified PP1 gamma 2 (the testis-specific isoform of PP1) as the only PP1 isoform in sperm and showed little protein phosphatase 2A (PP2A). In addition, of the known PP1 inhibitors, i.e., DARPP-32, inhibitor 1 (I1), and inhibitor 2 (I2), only I2-like activity was detected in sperm. Inhibition of PP1 by the heat-stable I2-like activity purified from sperm could be reversed with purified glycogen synthase kinase-3 (GSK-3). Furthermore, sperm extracts contain an inactive complex of PP1 and I2 (termed PP1I) that could also be activated by purified GSK-3. The presence of GSK-3 in sperm was demonstrated by activation of purified PP1I, and quantitation revealed that immotile caput sperm contained sixfold higher GSK-3 activity than motile caudal sperm. Immunoblot analysis confirmed the expression of GSK-3 in sperm and revealed the occurrence of both the alpha and beta isoforms. Our findings suggest that the higher PP1 activity measured in immotile sperm, presumably due to higher GSK-3 activity, is responsible for holding motility in check. This conclusion was supported by the observation that the phosphatase inhibitors OA and CA, at micromolar and nanomolar levels, respectively, were able to induce motility in completely immotile bovine caput epididymal sperm and to stimulate the kinetic activity of mature caudal sperm. The intrasperm levels of cAMP, pH, and calcium were unaltered by treatment with these inhibitors. The results suggest a biochemical basis for the development and regulation of sperm motility and a possible physiological role for the PP1/I2/GSK-3 system.

Overexpression of a Protein Phosphatase 2C from Beech Seeds in Arabidopsis Shows Phenotypes Related to Abscisic Acid Responses and Gibberellin Biosynthesis1

PubMed Central

Reyes, David; Rodríguez, Dolores; González-García, Mary Paz; Lorenzo, Oscar; Nicolás, Gregorio; García-Martínez, José Luis; Nicolás, Carlos

2006-01-01

A functional abscisic acid (ABA)-induced protein phosphatase type 2C (PP2C) was previously isolated from beech (Fagus sylvatica) seeds (FsPP2C2). Because transgenic work is not possible in beech, in this study we overexpressed this gene in Arabidopsis (Arabidopsis thaliana) to provide genetic evidence on FsPP2C2 function in seed dormancy and other plant responses. In contrast with other PP2Cs described so far, constitutive expression of FsPP2C2 in Arabidopsis, under the cauliflower mosaic virus 35S promoter, produced enhanced sensitivity to ABA and abiotic stress in seeds and vegetative tissues, dwarf phenotype, and delayed flowering, and all these effects were reversed by gibberellic acid application. The levels of active gibberellins (GAs) were reduced in 35S:FsPP2C2 plants, although transcript levels of AtGA20ox1 and AtGA3ox1 increased, probably as a result of negative feedback regulation, whereas the expression of GASA1 was induced by GAs. Additionally, FsPP2C2-overexpressing plants showed a strong induction of the Responsive to ABA 18 (RAB18) gene. Interestingly, FsPP2C2 contains two nuclear targeting sequences, and transient expression assays revealed that ABA directed this protein to the nucleus. Whereas other plant PP2Cs have been shown to act as negative regulators, our results support the hypothesis that FsPP2C2 is a positive regulator of ABA. Moreover, our results indicate the existence of potential cross-talk between ABA signaling and GA biosynthesis. PMID:16815952

Parallelism Effects and Verb Activation: The Sustained Reactivation Hypothesis

PubMed Central

Shapiro, Lewis P.; Love, Tracy

2010-01-01

This study investigated the processes underlying parallelism by evaluating the activation of a parallel element (i.e., a verb) throughout and-coordinated sentences. Four points were tested: (1) approximately 1,600ms after the verb in the first conjunct (PP1), (2) immediately following the conjunction (PP2), (3) approximately 1,100ms after the conjunction (PP3), (4) at the end of the second conjunct (PP4). The results revealed no activation at PP1, suggesting activation related to the initial presentation had decayed by this point; however, activation was observed at PP2, PP3, and PP4, suggesting the conjunction elicits reactivation that is sustained throughout the second conjunct. These findings support a specific hypothesis about parallelism, the sustained reactivation hypothesis. This hypothesis claims that, in conjoined structures, a cue that is associated with parallelism elicits the reactivation of material from the first conjunct and that this activation is sustained until integration with the second conjunct can be completed. PMID:19774464

Parallelism effects and verb activation: the sustained reactivation hypothesis.

PubMed

Callahan, Sarah M; Shapiro, Lewis P; Love, Tracy

2010-04-01

This study investigated the processes underlying parallelism by evaluating the activation of a parallel element (i.e., a verb) throughout and-coordinated sentences. Four points were tested: (1) approximately 1,600 ms after the verb in the first conjunct (PP1), (2) immediately following the conjunction (PP2), (3) approximately 1,100 ms after the conjunction (PP3), (4) at the end of the second conjunct (PP4). The results revealed no activation at PP1, suggesting activation related to the initial presentation had decayed by this point; however, activation was observed at PP2, PP3, and PP4, suggesting the conjunction elicits reactivation that is sustained throughout the second conjunct. These findings support a specific hypothesis about parallelism, the sustained reactivation hypothesis. This hypothesis claims that, in conjoined structures, a cue that is associated with parallelism elicits the reactivation of material from the first conjunct and that this activation is sustained until integration with the second conjunct can be completed.

Phosphorylation of mammalian Sgo2 by Aurora B recruits PP2A and MCAK to centromeres

PubMed Central

Tanno, Yuji; Kitajima, Tomoya S.; Honda, Takashi; Ando, Yasuto; Ishiguro, Kei-ichiro; Watanabe, Yoshinori

2010-01-01

Shugoshin (Sgo) is a conserved centromeric protein. Mammalian Sgo1 collaborates with protein phosphatase 2A (PP2A) to protect mitotic cohesin from the prophase dissociation pathway. Although another shugoshin-like protein, Sgo2, is required for the centromeric protection of cohesion in germ cells, its precise molecular function remains largely elusive. We demonstrate that hSgo2 plays a dual role in chromosome congression and centromeric protection of cohesion in HeLa cells, while the latter function is exposed only in perturbed mitosis. These functions partly overlap with those of Aurora B, a kinase setting faithful chromosome segregation. Accordingly, we identified the phosphorylation of hSgo2 by Aurora B at the N-terminal coiled-coil region and the middle region, and showed that these phosphorylations separately promote binding of hSgo2 to PP2A and MCAK, factors required for centromeric protection and chromosome congression, respectively. Furthermore, these phosphorylations are essential for localizing PP2A and MCAK to centromeres. This mechanism seems applicable to germ cells as well. Thus, our study identifies Sgo2 as a hitherto unknown crucial cellular substrate of Aurora B in mammalian cells. PMID:20889715

Analysis of the apiclutural industry in relation to geothermal development and agriculture in the Imperial Valley, Imperial County, California

DOE Office of Scientific and Technical Information (OSTI.GOV)

Atkins, E.L.

PART I: Continuous exposure to 30 ppB H/sub 2/S increased lifespan of caged worker honey bees, Apis mellifera L., 33%; whereas, bees exposed > 13 days to 100 ppB and 300 ppB H/sub 2/S the lifespan was shortened 32% and 51%, respectively, over unexposed bees; bees exposed > 15 days to a combination of 300 ppB H/sub 2/S + 50 ppM CO/sub 2/ the lifespan was shortened 4.4% more that 300 ppB H/sub 2/S alone. The mean temperature and/or relative humidity did not exert a direct effect on the hazard to bees. A continuous exposure to 300 ppB SO/sub 2/more » was detrimental to caged worker honey bees; and, a mean temperature of 27.2/sup 0/C was 75.7% more toxic than the same dosage at 16.7/sup 0/C. Worker bee lifespans exposed to 300 ppB SO/sub 2/ at 16.7/sup 0/C were shortened 13.5% and 79%, respectively, compared to unexposed bees. Therefore, both dosage and temperature exert direct effects on the hazards to bees. PART II: The status of the apicultural industry in Imperial County, California, was outlined giving a short characterization of the area in relation to the apicultural industry. Agriculture utilizes 500,000 intensely farmed acres which generated a 11-year average income of $370 million. Over 40 agricultural commodities are produced. The apicultural industry is intimately involved in 25% of the total gross agricultural income. In addition, most of the flora growing in the desert community which comprises the remainder of the county are very important to honey bees by providing sustaining nectar and/or pollen for brood rearing. The bee foraged flora provides substantial bee forage when colonies are located outside of the agriculutral area. It is concluded that geothermal resource development in the Imperial Valley is contemplated to have minimal effects on the apicultural industry.« less

Iron Bioavailability from Ferric Pyrophosphate in Extruded Rice Cofortified with Zinc Sulfate Is Greater than When Cofortified with Zinc Oxide in a Human Stable Isotope Study.

PubMed

Hackl, Laura; Zimmermann, Michael B; Zeder, Christophe; Parker, Megan; Johns, Paul W; Hurrell, Richard F; Moretti, Diego

2017-03-01

Background: Extruded rice grains are often cofortified with iron and zinc. However, it is uncertain if the addition of zinc to iron-fortified rice affects iron absorption and whether this is zinc-compound specific. Objective: We investigated whether zinc, added as zinc oxide (ZnO) or zinc sulfate (ZnSO 4 ), affects human iron absorption from extruded rice fortified with ferric pyrophosphate (FePP). Methods: In 19 iron-depleted Swiss women (plasma ferritin ≤16.5 μ/L) aged between 20 and 39 y with a normal body mass index (in kg/m 2 ; 18.7-24.8), we compared iron absorption from 4 meals containing fortified extruded rice with 4 mg Fe and 3 mg Zn. Three of the meals contained extruded rice labeled with FePP ( 57 FePP): 1 ) 1 meal without added zinc ( 57 FePP-Zn), 2 ) 1 cofortified with ZnO ( 57 FePP+ZnO), and 3 ) 1 cofortified with ZnSO 4 ( 57 FePP+ZnSO 4 ). The fourth meal contained extruded rice without iron or zinc, extrinsically labeled with ferrous sulfate ( 58 FeSO 4 ) added as a solution after cooking. All 4 meals contained citric acid. Iron bioavailability was measured by isotopic iron ratios in red blood cells. We also measured relative in vitro iron solubility from 57 FePP-Zn, 57 FePP+ZnO, and 57 FePP+ZnSO 4 expressed as a fraction of FeSO 4 solubility. Results: Geometric mean fractional iron absorption (95% CI) from 57 FePP+ZnSO 4 was 4.5% (3.4%, 5.8%) and differed from 57 FePP+ZnO (2.7%; 1.8%, 4.1%) ( P < 0.03); both did not differ from 57 FePP-Zn: 4.0% (2.8%, 5.6%). Relative iron bioavailabilities compared with 58 FeSO 4 were 62%, 57%, and 38% from 57 FePP+ZnSO 4 , 57 FePP-Zn, and 57 FePP+ZnO, respectively. In vitro solubility from 57 FePP+ZnSO 4 differed from that of 57 FePP-Zn (14.3%; P < 0.02) but not from that of 57 FePP+ZnO (10.2% compared with 13.1%; P = 0.08). Conclusions: In iron-depleted women, iron absorption from FePP-fortified extruded rice cofortified with ZnSO 4 was 1.6-fold (95% CI: 1.4-, 1.9-fold) that of rice cofortified with ZnO. These findings suggest that ZnSO 4 may be the preferable zinc cofortificant for optimal iron bioavailability of iron-fortified extruded rice. This trial was registered at clinicaltrials.gov as NCT02255942. © 2017 American Society for Nutrition.

Nuclear-cytoplasmic shuttling protein PP2AB56 contributes to mTORC1-dependent dephosphorylation of FOXK1.

PubMed

Nakatsumi, Hirokazu; Oka, Takeru; Higa, Tsunaki; Shirane, Michiko; Nakayama, Keiichi I

2018-05-29

Mammalian target of rapamycin complex 1 (mTORC1) kinase is a master regulator of the cellular response to nutrition-related signals such as insulin and amino acids. mTORC1 is activated on the lysosomal membrane and induces phosphorylation of a variety of downstream molecules. We previously showed that activated mTORC1 induces protein phosphatase 2A (PP2A)-mediated dephosphorylation of the transcription factor forkhead box K1 (FOXK1). The mechanism underlying the signal transduction from the cytoplasmic mTORC1 to the nuclear FOXK1 has remained unclear, however, we now show that a nuclear-cytoplasmic transport system is necessary for the mTORC1-FOXK1 signal transduction. This reaction is mediated by a shuttling protein B56, which is a regulatory subunit of PP2A and plays an essential role in the mTORC1-dependent dephosphorylation of FOXK1. These results suggest that PP2A B56 phosphatase contributes to the signaling for mTORC1-dependent transcriptional regulation. © 2018 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

Decoration of Silica Nanoparticles on Polypropylene Separator for Lithium-Sulfur Batteries.

PubMed

Li, Jing; Huang, Yudai; Zhang, Su; Jia, Wei; Wang, Xingchao; Guo, Yong; Jia, Dianzeng; Wang, Lishi

2017-03-01

A SiO 2 nanoparticle decorated polypropylene (PP) separator (PP-SiO 2 ) has been prepared by simply immersing the PP separator in the hydrolysis solution of tetraethyl orthosilicate (TEOS) with the assistance of Tween-80. After decoration, the thermal stability and the electrolyte wettability of the PP-SiO 2 separator are obviously improved. When the PP-SiO 2 separator is used for lithium-sulfur (Li-S) batteries, the cyclic stability and rate capability of the batteries are greatly enhanced. The capacity retention ratio of the Li-S battery configured with the PP-SiO 2 separator is 64% after 200 cycles at 0.2 C, which is much higher than that configured with the PP separator (45%). Moreover, the rate capacity of the Li-S batteries using the PP-SiO 2 separator reaches 956.3, 691.5, 621, and 567.6 mAh g -1 at the current density of 0.2, 0.5, 1, and 2 C, respectively. The reason could be ascribed to that the polar silica coating not only alleviates the shuttle effect but also facilitates Li-ion migration.

Tidal Dissipation in a Homogeneous Spherical Body. 2. Three Examples: Mercury, IO, and Kepler-10 b

DTIC Science & Technology

2014-11-01

The Astrophysical Journal, 795:7 (10pp), 2014 November 1 doi:10.1088/0004-637X/795/1/7 C© 2014. The American Astronomical Society. All rights...public release; distribution unlimited 13. SUPPLEMENTARY NOTES The Astrophysical Journal, 795:7 (10pp), 2014 November 1 14. ABSTRACT 15. SUBJECT... Astrophysical Journal, 795:7 (10pp), 2014 November 1 Makarov & Efroimsky a, e, i, ω, Ω, M, which are the semimajor axis, eccentricity, inclination

Recombinant α- β- and γ-Synucleins Stimulate Protein Phosphatase 2A Catalytic Subunit Activity in Cell Free Assays

PubMed Central

Lek, Sovanarak; Vargas-Medrano, Javier; Villanueva, Ernesto; Marcus, Brian; Godfrey, Wesley; Perez, Ruth G.

2017-01-01

α-Synuclein (aSyn), β-Synuclein (bSyn), and γ-Synuclein (gSyn) are members of a conserved family of chaperone-like proteins that are highly expressed in vertebrate neuronal tissues. Of the three synucleins, only aSyn has been strongly implicated in neurodegenerative disorders such as Parkinson's disease, Dementia with Lewy Bodies, and Multiple System Atrophy. In studying normal aSyn function, data indicate that aSyn stimulates the activity of the catalytic subunit of an abundantly expressed dephosphorylating enzyme, PP2Ac in vitro and in vivo. Prior data show that aSyn aggregation in human brain reduces PP2Ac activity in regions with Lewy body pathology, where soluble aSyn has become insoluble. However, because all three synucleins have considerable homology in the amino acid sequences, experiments were designed to test if all can modulate PP2Ac activity. Using recombinant synucleins and recombinant PP2Ac protein, activity was assessed by malachite green colorimetric assay. Data revealed that all three recombinant synucleins stimulated PP2Ac activity in cell-free assays, raising the possibility that the conserved homology between synucleins may endow all three homologs with the ability to bind to and activate the PP2Ac. Co-immunoprecipitation data, however, suggest that PP2Ac modulation likely occurs through endogenous interactions between aSyn and PP2Ac in vivo. PMID:28829427

An Empirical Examination of Reverse Auction Appropriateness in B2B Source Selection

DTIC Science & Technology

2006-01-01

Measures of Marketing Constructs," Journal of Marketing Research , Vol. 16, No.2, pp. 64 - 73. Cohn, L. (2000), "B2B: The Hottest Net Bet Yet...34 Psycholgical Bulletin, Vol. 103, No.3, pp. 411-423. Armstrong, J.S. and T.S. Overton (1977), "Estimating Nonresponse Bias in Mail Surveys," Journal of Marketing ... Research , Vol.14, No.3, pp. 396-402. Bagozzi, R. (1983), "Issues in the Application of Covariance Structure Analysis: A Further Comment," Journal of

Epigallocatechin-3-gallate and penta-O-galloyl-β-D-glucose inhibit protein phosphatase-1.

PubMed

Kiss, Andrea; Bécsi, Bálint; Kolozsvári, Bernadett; Komáromi, István; Kövér, Katalin E; Erdődi, Ferenc

2013-01-01

Protein phosphatase-1 (PP1) and protein phosphatase-2A (PP2A) are responsible for the dephosphorylation of the majority of phosphoserine/threonine residues in cells. In this study, we show that (-)-epigallocatechin-3-gallate (EGCG) and 1,2,3,4,6-penta-O-galloyl-β-D-glucose (PGG), polyphenolic constituents of green tea and tannins, inhibit the activity of the PP1 recombinant δ-isoform of the PP1 catalytic subunit and the native PP1 catalytic subunit (PP1c) with IC(50) values of 0.47-1.35 μm and 0.26-0.4 μm, respectively. EGCG and PGG inhibit PP2Ac less potently, with IC(50) values of 15 and 6.6 μm, respectively. The structure-inhibitory potency relationships of catechin derivatives suggests that the galloyl group may play a major role in phosphatase inhibition. The interaction of EGCG and PGG with PP1c was characterized by NMR and surface plasmon resonance-based binding techniques. Competitive binding assays and molecular modeling suggest that EGCG docks at the hydrophobic groove close to the catalytic center of PP1c, partially overlapping with the binding surface of microcystin-LR or okadaic acid. This hydrophobic interaction is further stabilized by hydrogen bonding via hydroxyl/oxo groups of EGCG to PP1c residues. Comparative docking shows that EGCG binds to PP2Ac in a similar manner, but in a distinct pose. Long-term treatment (24 h) with these compounds and other catechins suppresses the viability of HeLa cells with a relative effectiveness reminiscent of their in vitro PP1c-inhibitory potencies. The above data imply that the phosphatase-inhibitory features of these polyphenols may be implicated in the wide spectrum of their physiological influence. © 2012 The Authors Journal compilation © 2012 FEBS.

Protein phosphatase 2A associates with and regulates atypical PKC and the epithelial tight junction complex

PubMed Central

Nunbhakdi-Craig, Viyada; Machleidt, Thomas; Ogris, Egon; Bellotto, Dennis; White, Charles L.; Sontag, Estelle

2002-01-01

Tight junctions (TJs) play a crucial role in the establishment of cell polarity and regulation of paracellular permeability in epithelia. Here, we show that upon calcium-induced junction biogenesis in Madin-Darby canine kidney cells, ABαC, a major protein phosphatase (PP)2A holoenzyme, is recruited to the apical membrane where it interacts with the TJ complex. Enhanced PP2A activity induces dephosphorylation of the TJ proteins, ZO-1, occludin, and claudin-1, and is associated with increased paracellular permeability. Expression of PP2A catalytic subunit severely prevents TJ assembly. Conversely, inhibition of PP2A by okadaic acid promotes the phosphorylation and recruitment of ZO-1, occludin, and claudin-1 to the TJ during junctional biogenesis. PP2A negatively regulates TJ assembly without appreciably affecting the organization of F-actin and E-cadherin. Significantly, inhibition of atypical PKC (aPKC) blocks the calcium- and serum-independent membrane redistribution of TJ proteins induced by okadaic acid. Indeed, PP2A associates with and critically regulates the activity and distribution of aPKC during TJ formation. Thus, we provide the first evidence for calcium-dependent targeting of PP2A in epithelial cells, we identify PP2A as the first serine/threonine phosphatase associated with the multiprotein TJ complex, and we unveil a novel role for PP2A in the regulation of epithelial aPKC and TJ assembly and function. PMID:12196510

Characterization of pumpkin polysaccharides and protective effects on streptozotocin-damaged islet cells.

PubMed

Zhu, Hong-Yan; Chen, Guang-Tong; Meng, Guo-Liang; Xu, Ji-Liang

2015-03-01

The polysaccharides from pumpkin fruit (PP) were obtained and purified by hot-water extraction, anion-exchange chromatography, and gel column chromatography. The physicochemical properties of PP were determined by gel filtration chromatography, gas chromatography, fourier transform infrared (FTIR) spectroscopy, and nuclear magnetic resonance (NMR) spectroscopy. Results indicated that the molecular weight of PP was about 23 kDa and PP was composed of D-Arabinose, D-Mannose, D-Glucose, and D-Galactose with a molar ratio of 1 : 7.79 : 70.32 : 7.05. FTIR and NMR spectra indicated that PP was the polysaccharide containing pyranose ring. Additionally, PP protected islets cells from streptozotocin (STZ) injury in vitro via increasing the levels of super-oxide dismutase (SOD) and malondialdehyde (MDA) and reducing the production of NO. The experiment of reverse transcriptase-polymerase chain reaction further proved that PP inhibited apoptosis via modulating the expression of Bax/Bcl-2 in STZ-damaged islet cells. In conclusion, PP could be explored as a novel agent for the treatment of diabetes mellitus. Copyright © 2015 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Differential regulation of protein phosphatase 1 (PP1) isoforms in human heart failure and atrial fibrillation.

PubMed

Meyer-Roxlau, Stefanie; Lämmle, Simon; Opitz, Annett; Künzel, Stephan; Joos, Julius P; Neef, Stefan; Sekeres, Karolina; Sossalla, Samuel; Schöndube, Friedrich; Alexiou, Konstantin; Maier, Lars S; Dobrev, Dobromir; Guan, Kaomei; Weber, Silvio; El-Armouche, Ali

2017-07-01

Protein phosphatase 1 (PP1) is a key regulator of important cardiac signaling pathways. Dysregulation of PP1 has been heavily implicated in cardiac dysfunctions. Accordingly, pharmacological targeting of PP1 activity is considered for therapeutic intervention in human cardiomyopathies. Recent evidence from animal models implicated previously unrecognized, isoform-specific activities of PP1 in the healthy and diseased heart. Therefore, this study examined the expression of the distinct PP1 isoforms PP1α, β, and γ in human heart failure (HF) and atrial fibrillation (AF) and addressed the consequences of β-adrenoceptor blocker (beta-blocker) therapy for HF patients with reduced ejection fraction on PP1 isoform expression. Using western blot analysis, we found greater abundance of PP1 isoforms α and γ but unaltered PP1β levels in left ventricular myocardial tissues from HF patients as compared to non-failing controls. However, expression of all three PP1 isoforms was higher in atrial appendages from patients with AF compared to patients with sinus rhythm. Moreover, we found that in human failing ventricles, beta-blocker therapy was associated with lower PP1α abundance and activity, as indicated by higher phosphorylation of the PP1α-specific substrate eIF2α. Greater eIF2α phosphorylation is a known repressor of protein translation, and accordingly, we found lower levels of the endoplasmic reticulum (ER) stress marker Grp78 in the very same samples. We propose that isoform-specific targeting of PP1α activity may be a novel and innovative therapeutic strategy for the treatment of human cardiac diseases by reducing ER stress conditions.

Identification of residues within the African swine fever virus DP71L protein required for dephosphorylation of translation initiation factor eIF2α and inhibiting activation of pro-apoptotic CHOP

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barber, Claire; Netherton, Chris; Goatley, Lynnett

The African swine fever virus DP71L protein recruits protein phosphatase 1 (PP1) to dephosphorylate the translation initiation factor 2α (eIF2α) and avoid shut-off of global protein synthesis and downstream activation of the pro-apoptotic factor CHOP. Residues V16 and F18A were critical for binding of DP71L to PP1. Mutation of this PP1 binding motif or deletion of residues between 52 and 66 reduced the ability of DP71L to cause dephosphorylation of eIF2α and inhibit CHOP induction. The residues LSAVL, between 57 and 61, were also required. PP1 was co-precipitated with wild type DP71L and the mutant lacking residues 52- 66 ormore » the LSAVL motif, but not with the PP1 binding motif mutant. The residues in the LSAVL motif play a critical role in DP71L function but do not interfere with binding to PP1. Instead we propose these residues are important for DP71L binding to eIF2α. - Highlights: •The African swine fever virus DP71L protein recruits protein phosphatase 1 (PP1) to dephosphorylate translation initiation factor eIF2α (eIF2α). •The residues V{sup 16}, F{sup 18} of DP71L are required for binding to the α, β and γ isoforms of PP1 and for DP71L function. •The sequence LSAVL downstream from the PP1 binding site (residues 57–61) are also important for DP71L function. •DP71L mutants of the LSAVL sequence retain ability to co-precipitate with PP1 showing these sequences have a different role to PP1 binding.« less

Mutations in the PP2A regulatory subunit B family genes PPP2R5B, PPP2R5C and PPP2R5D cause human overgrowth.

PubMed

Loveday, Chey; Tatton-Brown, Katrina; Clarke, Matthew; Westwood, Isaac; Renwick, Anthony; Ramsay, Emma; Nemeth, Andrea; Campbell, Jennifer; Joss, Shelagh; Gardner, McKinlay; Zachariou, Anna; Elliott, Anna; Ruark, Elise; van Montfort, Rob; Rahman, Nazneen

2015-09-01

Overgrowth syndromes comprise a group of heterogeneous disorders characterised by excessive growth parameters, often in association with intellectual disability. To identify new causes of human overgrowth, we have been undertaking trio-based exome sequencing studies in overgrowth patients and their unaffected parents. Prioritisation of functionally relevant genes with multiple unique de novo mutations revealed four mutations in protein phosphatase 2A (PP2A) regulatory subunit B family genes protein phosphatase 2, regulatory Subunit B', beta (PPP2R5B); protein phosphatase 2, regulatory Subunit B', gamma (PPP2R5C); and protein phosphatase 2, regulatory Subunit B', delta (PPP2R5D). This observation in 3 related genes in 111 individuals with a similar phenotype is greatly in excess of the expected number, as determined from gene-specific de novo mutation rates (P = 1.43 × 10(-10)). Analysis of exome-sequencing data from a follow-up series of overgrowth probands identified a further pathogenic mutation, bringing the total number of affected individuals to 5. Heterozygotes shared similar phenotypic features including increased height, increased head circumference and intellectual disability. The mutations clustered within a region of nine amino acid residues in the aligned protein sequences (P = 1.6 × 10(-5)). We mapped the mutations onto the crystal structure of the PP2A holoenzyme complex to predict their molecular and functional consequences. These studies suggest that the mutations may affect substrate binding, thus perturbing the ability of PP2A to dephosphorylate particular protein substrates. PP2A is a major negative regulator of v-akt murine thymoma viral oncogene homolog 1 (AKT). Thus, our data further expand the list of genes encoding components of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT signalling cascade that are disrupted in human overgrowth conditions. © The Author 2015. Published by Oxford University Press.

The effects of first gestation and lactation on bone metabolism in dairy goats and milk sheep.

PubMed

Liesegang, A; Risteli, J; Wanner, M

2006-06-01

The goal of the present study was to compare mobilization rate of calcium (Ca) from bone in pregnant and lactating goats and sheep. Blood samples were collected from goats and sheep monthly during pregnancy and at 1, 2, and 4 weeks postpartum (pp) and monthly during lactation until 6 months after parturition. Total bone mineral content (BMC) and total bone mineral density (BMD) were quantified using peripheral quantitative computed tomography at the same intervals as the blood was taken. Bone resorption was assessed by immunoassays quantitating two epitopes of the carboxyterminal telopeptide of type I collagen (ICTP, CTX). Bone formation was estimated by quantifying serum osteocalcin (OC) and bone-specific alkaline phosphatase (bAP). In addition, Ca and 1,25-dihydroxy vitamin D (1,25-VITD) concentrations were determined in serum. Mean ICTP and CTX concentrations of both animal species increased the first week after parturition. By the second week pp, the concentrations of both markers had decreased toward early gestation levels. In contrast, mean OC concentrations continually decreased until the 1st week pp. By the 2nd week pp, the mean concentrations of OC started to increase again. Mean bAP activities decreased during gestation and reached a nadir in the first week pp in goats and 4 weeks pp in sheep. Afterwards, mean bAP activities increased again in goats and sheep. 1,25-VITD concentrations peaked the first week pp and returned to early gestation values thereafter. Total BMC and BMD decreased from the 4th month of pregnancy until the 1st week pp in both species. Afterwards, BMC increased throughout the first month pp in goats and the first 3 months pp in sheep. BMD levels of sheep and goats returned to prepartum levels during lactation. The resorptive phase of bone remodeling is accelerated at parturition and in early lactation and is uncoupled from the process of bone formation. This allows the animal to achieve Ca homeostasis at the expense of bone. Increased bone remodeling during lactation may represent physiological mechanisms to help replace the maternal skeleton lost as the animal adapted to enormously increased Ca losses to the fetus and milk in late gestation and early lactation.

Cloning and expression profiling of the PacSnRK2 and PacPP2C gene families during fruit development, ABA treatment, and dehydration stress in sweet cherry.

PubMed

Shen, Xinjie; Guo, Xiao; Zhao, Di; Zhang, Qiang; Jiang, Yuzhuang; Wang, Yantao; Peng, Xiang; Wei, Yan; Zhai, Zefeng; Zhao, Wei; Li, Tianhong

2017-10-01

Plant SNF1-related protein kinase 2 (SnRK2) and protein phosphatase 2C (PP2C) family members are core components of the ABA signal transduction pathway. SnRK2 and PP2C proteins have been suggested to play crucial roles in fruit ripening and improving plant tolerance to drought stress, but supporting genetic information has been lacking in sweet cherry (Prunus avium L.). Here, we cloned six full-length SnRK2 genes and three full-length PP2C genes from sweet cherry cv. Hong Deng. Quantitative PCR analysis revealed that PacSnRK2.2, PacSnRK2.3, PacSnRK2.6, and PacPP2C1-3 were negatively regulated in fruits in response to exogenous ABA treatment, PacSnRK2.4 and PacSnRK2.5 were upregulated, and PacSnRK2.1 expression was not affected. The ABA treatment also significantly promoted the accumulation of anthocyanins in sweet cherry fruit. The expression of all PacSnRK2 and PacPP2C genes was induced by dehydration stress, which also promoted the accumulation of drought stress signaling molecules in the sweet cherry fruits, including ABA, soluble sugars, and anthocyanin. Furthermore, a yeast two-hybrid analysis demonstrated that PacPP2C1 interacts with all six PacSnRK2s, while PacPP2C3 does not interact with PacSnRK2.5. PacPP2C2 does not interact with PacSnRK2.1 or PacSnRK2.4. These results indicate that PacSnRK2s and PacPP2Cs may play a variety of roles in the sweet cherry ABA signaling pathway and the fruit response to drought stress. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Coated 4340 Steel

DTIC Science & Technology

2013-08-26

Magazine, 2004, Vol. 60, No. 68, pp. 7-11. 2. A. Wrigley: Aerospace Metals, American Metal Market , of May 1994. 3. L. L. Sherir: in Corrosion 1...Electrochemistry and Engineering, ASTM STP 801, T. W. Crooker and B. N Leis, Eds., American Society for Testing and Materials, 1983, pp. 5-25. 8. B. Fitzsimons

Genome-wide characterization of vibrio phage ϕpp2 with unique arrangements of the mob-like genes

PubMed Central

2012-01-01

Background Vibrio parahaemolyticus is associated with gastroenteritis, wound infections, and septicemia in human and animals. Phages can control the population of the pathogen. So far, the only one reported genome among giant vibriophages is KVP40: 244,835 bp with 26% coding regions that have T4 homologs. Putative homing endonucleases (HE) were found in Vibrio phage KVP40 bearing one segD and Vibrio cholerae phage ICP1 carrying one mobC/E and one segG. Results A newly isolated Vibrio phage ϕpp2, which was specific to the hosts of V. parahaemolyticus and V. alginolyticus, featured a long nonenveloped head of ~90 × 150 nm and tail of ~110 nm. The phage can survive at 50°C for more than one hour. The genome of the phage ϕpp2 was sequenced to be 246,421 bp, which is 1587 bp larger than KVP40. 383 protein-encoding genes (PEGs) and 30 tRNAs were found in the phage ϕpp2. Between the genomes of ϕpp2 and KVP40, 254 genes including 29 PEGs for viral structure were of high similarity, whereas 17 PEGs of KVP40 and 21 PEGs of ϕpp2 were unmatched. In both genomes, the capsid and tail genes have been identified, as well as the extensive representation of the DNA replication, recombination, and repair enzymes. In addition to the three giant indels of 1098, 1143 and 3330 nt, ϕpp2 possessed unique proteins involved in potassium channel, gp2 (DNA end protector), tRNA nucleotidyltransferase, and mob-type HEs, which were not reported in KVP40. The ϕpp2 PEG274, with strong promoters and translational initiation, was identified to be a mobE type, flanked by NrdA and NrdB/C homologs. Coincidently, several pairs of HE-flanking homologs with empty center were found in the phages of Vibrio phages ϕpp2 and KVP40, as well as in Aeromonas phages (Aeh1 and Ae65), and cyanophage P-SSM2. Conclusions Vibrio phage ϕpp2 was characterized by morphology, growth, and genomics with three giant indels and different types of HEs. The gene analysis on the required elements for transcription and translation suggested that the ϕpp2 PEG274 was an active mobE gene. The phage was signified to be a new species of T4-related, differing from KVP40. PMID:22676552

Interleukin-18 gene deletion protects against sepsis-induced cardiac dysfunction by inhibiting PP2A activity.

PubMed

Okuhara, Yoshitaka; Yokoe, Shunichi; Iwasaku, Toshihiro; Eguchi, Akiyo; Nishimura, Koichi; Li, Wen; Oboshi, Makiko; Naito, Yoshiro; Mano, Toshiaki; Asahi, Michio; Okamura, Haruki; Masuyama, Tohru; Hirotani, Shinichi

2017-09-15

Interleukin-18 (IL-18) neutralization protects against lipopolysaccharide (LPS)-induced injuries, including myocardial dysfunction. However, the mechanism is yet to be fully elucidated. The aim of the present study was to determine whether IL-18 gene deletion prevents sepsis-induced cardiac dysfunction and to elucidate the potential mechanisms underlying IL-18-mediated cardiotoxicity by LPS. Ten-week-old male wild-type (WT) and IL-18 knockout (IL-18 KO) mice were intraperitoneally administered LPS. Serial echocardiography showed better systolic pump function and less left ventricular (LV) dilatation in LPS-treated IL-18 KO mice compared with those in LPS-treated WT mice. LPS treatment significantly decreased the levels of phospholamban (PLN) and Akt phosphorylation in WT mice compared with those in saline-treated WT mice, while the LPS-induced decrease in the phosphorylation levels was attenuated in IL-18 KO mice compared with that in WT mice. IL-18 gene deletion also attenuated an LPS-induced increase of type 2 protein phosphatase 2A (PP2A) activity, a molecule that dephosphorylates PLN and Akt. There was no difference in type 1 protein phosphatase (PP1) activity. To address whether IL-18 affects PLN and Akt phosphorylation via PP2A activation in cardiomyocytes, rat neonatal cardiac myocytes were cultured and stimulated using 100ng/ml of recombinant rat IL-18. Exogenous IL-18 decreased the level of PLN and Akt phosphorylation in cardiomyocytes. PP2A activity but not PP1 activity was increased by IL-18 stimulation in cardiomyocytes. IL-18 plays a pivotal role in advancing sepsis-induced cardiac dysfunction, and the mechanisms underlying IL-18-mediated cardiotoxicity potentially involve the regulation of PLN and Akt phosphorylation through PP2A activity. Copyright © 2017 Elsevier B.V. All rights reserved.

Protein Phosphatase-1 Inhibitor-2 Is a Novel Memory Suppressor.

PubMed

Yang, Hongtian; Hou, Hailong; Pahng, Amanda; Gu, Hua; Nairn, Angus C; Tang, Ya-Ping; Colombo, Paul J; Xia, Houhui

2015-11-11

Reversible phosphorylation, a fundamental regulatory mechanism required for many biological processes including memory formation, is coordinated by the opposing actions of protein kinases and phosphatases. Type I protein phosphatase (PP1), in particular, has been shown to constrain learning and memory formation. However, how PP1 might be regulated in memory is still not clear. Our previous work has elucidated that PP1 inhibitor-2 (I-2) is an endogenous regulator of PP1 in hippocampal and cortical neurons (Hou et al., 2013). Contrary to expectation, our studies of contextual fear conditioning and novel object recognition in I-2 heterozygous mice suggest that I-2 is a memory suppressor. In addition, lentiviral knock-down of I-2 in the rat dorsal hippocampus facilitated memory for tasks dependent on the hippocampus. Our data indicate that I-2 suppresses memory formation, probably via negatively regulating the phosphorylation of cAMP/calcium response element-binding protein (CREB) at serine 133 and CREB-mediated gene expression in dorsal hippocampus. Surprisingly, the data from both biochemical and behavioral studies suggest that I-2, despite its assumed action as a PP1 inhibitor, is a positive regulator of PP1 function in memory formation. We found that inhibitor-2 acts as a memory suppressor through its positive functional influence on type I protein phosphatase (PP1), likely resulting in negative regulation of cAMP/calcium response element-binding protein (CREB) and CREB-activated gene expression. Our studies thus provide an interesting example of a molecule with an in vivo function that is opposite to its in vitro function. PP1 plays critical roles in many essential physiological functions such as cell mitosis and glucose metabolism in addition to its known role in memory formation. PP1 pharmacological inhibitors would thus not be able to serve as good therapeutic reagents because of its many targets. However, identification of PP1 inhibitor-2 as a critical contributor to suppression of memory formation by PP1 may provide a novel therapeutic target for memory-related diseases. Copyright © 2015 the authors 0270-6474/15/3515082-06$15.00/0.

The geographical distribution and prevalence of Echinococcus multilocularis in animals in the European Union and adjacent countries: a systematic review and meta-analysis.

PubMed

Oksanen, Antti; Siles-Lucas, Mar; Karamon, Jacek; Possenti, Alessia; Conraths, Franz J; Romig, Thomas; Wysocki, Patrick; Mannocci, Alice; Mipatrini, Daniele; La Torre, Giuseppe; Boufana, Belgees; Casulli, Adriano

2016-09-28

This study aimed to provide a systematic review on the geographical distribution of Echinococcus multilocularis in definitive and intermediate hosts in the European Union (EU) and adjacent countries (AC). The relative importance of the different host species in the life-cycle of this parasite was highlighted and gaps in our knowledge regarding these hosts were identified. Six databases were searched for primary research studies published from 1900 to 2015. From a total of 2,805 identified scientific papers, 244 publications were used for meta-analyses. Studies in 21 countries reported the presence of E. multilocularis in red foxes, with the following pooled prevalence (PP): low (≤ 1 %; Denmark, Slovenia and Sweden); medium (> 1 % to < 10 %; Austria, Belgium, Croatia, Hungary, Italy, the Netherlands, Romania and the Ukraine); and high (> 10 %; Czech Republic, Estonia, France, Germany, Latvia, Lithuania, Poland, Slovakia, Liechtenstein and Switzerland). Studies from Finland, Ireland, the United Kingdom and Norway reported the absence of E. multilocularis in red foxes. However, E. multilocularis was detected in Arctic foxes from the Arctic Archipelago of Svalbard in Norway. Raccoon dogs (PP 2.2 %), golden jackals (PP 4.7 %) and wolves (PP 1.4 %) showed a higher E. multilocularis PP than dogs (PP 0.3 %) and cats (PP 0.5 %). High E. multilocularis PP in raccoon dogs and golden jackals correlated with high PP in foxes. For intermediate hosts (IHs), muskrats (PP 4.2 %) and arvicolids (PP 6.0 %) showed similar E. multilocularis PP as sylvatic definitive hosts (DHs), excluding foxes. Nutrias (PP 1.0 %) and murids (PP 1.1 %) could play a role in the life-cycle of E. multilocularis in areas with medium to high PP in red foxes. In areas with low PP in foxes, no other DH was found infected with E. multilocularis. When fox E. multilocularis PP was >3 %, raccoon dogs and golden jackals could play a similar role as foxes. In areas with high E. multilocularis fox PP, the wolf emerged as a potentially important DH. Dogs and cats could be irrelevant in the life-cycle of the parasite in Europe, although dogs could be important for parasite introduction into non-endemic areas. Muskrats and arvicolids are important IHs. Swine, insectivores, murids and nutrias seem to play a minor or no role in the life-cycle of the parasite within the EU and ACs.

Cell cycle-dependent regulation of Greatwall kinase by protein phosphatase 1 and regulatory subunit 3B.

PubMed

Ren, Dapeng; Fisher, Laura A; Zhao, Jing; Wang, Ling; Williams, Byron C; Goldberg, Michael L; Peng, Aimin

2017-06-16

Greatwall (Gwl) kinase plays an essential role in the regulation of mitotic entry and progression. Mitotic activation of Gwl requires both cyclin-dependent kinase 1 (CDK1)-dependent phosphorylation and its autophosphorylation at an evolutionarily conserved serine residue near the carboxyl terminus (Ser-883 in Xenopus ). In this study we show that Gwl associates with protein phosphatase 1 (PP1), particularly PP1γ, which mediates the dephosphorylation of Gwl Ser-883. Consistent with the mitotic activation of Gwl, its association with PP1 is disrupted in mitotic cells and egg extracts. During mitotic exit, PP1-dependent dephosphorylation of Gwl Ser-883 occurs prior to dephosphorylation of other mitotic substrates; replacing endogenous Gwl with a phosphomimetic S883E mutant blocks mitotic exit. Moreover, we identified PP1 regulatory subunit 3B (PPP1R3B) as a targeting subunit that can direct PP1 activity toward Gwl. PPP1R3B bridges PP1 and Gwl association and promotes Gwl Ser-883 dephosphorylation. Consistent with the cell cycle-dependent association of Gwl and PP1, Gwl and PPP1R3B dissociate in M phase. Interestingly, up-regulation of PPP1R3B facilitates mitotic exit and blocks mitotic entry. Thus, our study suggests PPP1R3B as a new cell cycle regulator that functions by governing Gwl dephosphorylation. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

The Zds proteins control entry into mitosis and target protein phosphatase 2A to the Cdc25 phosphatase.

PubMed

Wicky, Sidonie; Tjandra, Hendri; Schieltz, David; Yates, John; Kellogg, Douglas R

2011-01-01

The Wee1 kinase restrains entry into mitosis by phosphorylating and inhibiting cyclin-dependent kinase 1 (Cdk1). The Cdc25 phosphatase promotes entry into mitosis by removing Cdk1 inhibitory phosphorylation. Experiments in diverse systems have established that Wee1 and Cdc25 are regulated by protein phosphatase 2A (PP2A), but a full understanding of the function and regulation of PP2A in entry into mitosis has remained elusive. In budding yeast, entry into mitosis is controlled by a specific form of PP2A that is associated with the Cdc55 regulatory subunit (PP2A(Cdc55)). We show here that related proteins called Zds1 and Zds2 form a tight stoichiometric complex with PP2A(Cdc55) and target its activity to Cdc25 but not to Wee1. Conditional inactivation of the Zds proteins revealed that their function is required primarily at entry into mitosis. In addition, Zds1 undergoes cell cycle-dependent changes in phosphorylation. Together, these observations define a role for the Zds proteins in controlling specific functions of PP2A(Cdc55) and suggest that upstream signals that regulate PP2A(Cdc55) may play an important role in controlling entry into mitosis.

Structural basis of PP2A activation by PTPA, an ATP-dependent activation chaperone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo, Feng; Stanevich, Vitali; Wlodarchak, Nathan

Proper activation of protein phosphatase 2A (PP2A) catalytic subunit is central for the complex PP2A regulation and is crucial for broad aspects of cellular function. The crystal structure of PP2A bound to PP2A phosphatase activator (PTPA) and ATPγS reveals that PTPA makes broad contacts with the structural elements surrounding the PP2A active site and the adenine moiety of ATP. PTPA-binding stabilizes the protein fold of apo-PP2A required for activation, and orients ATP phosphoryl groups to bind directly to the PP2A active site. This allows ATP to modulate the metal-binding preferences of the PP2A active site and utilize the PP2A activemore » site for ATP hydrolysis. In vitro, ATP selectively and drastically enhances binding of endogenous catalytic metal ions, which requires ATP hydrolysis and is crucial for acquisition of pSer/Thr-specific phosphatase activity. Furthermore, both PP2A- and ATP-binding are required for PTPA function in cell proliferation and survival. Our results suggest novel mechanisms of PTPA in PP2A activation with structural economy and a unique ATP-binding pocket that could potentially serve as a specific therapeutic target.« less

Search for Higgs boson pair production in the bb¯bb¯ final state from pp collision at √s = 8 TeV with the ATLAS detector

DOE PAGES

Aad, G.

2015-09-09

A search for Higgs boson pair production \\(pp \\rightarrow hh\\) is performed with 19.5 fb\\(^{-1}\\) of proton–proton collision data at \\(\\sqrt{s}=8\\) TeV, which were recorded by the ATLAS detector at the Large Hadron Collider in 2012. The decay products of each Higgs boson are reconstructed as a high-momentum \\(b\\bar{b}\\) system with either a pair of small-radius jets or a single large-radius jet, the latter exploiting jet substructure techniques and associated b-tagged track-jets. No evidence for resonant or non-resonant Higgs boson pair production is observed. The data are interpreted in the context of the Randall–Sundrum model with a warped extra dimensionmore » as well as the two-Higgs-doublet model. An upper limit on the cross-section for \\(pp\\rightarrow G^{*}_{\\mathrm {KK}} \\rightarrow hh \\rightarrow b\\bar{b}b\\bar{b} \\) of 3.2 (2.3) fb is set for a Kaluza–Klein graviton \\(G^{*}_{\\mathrm {KK}}\\) mass of 1.0 (1.5) TeV, at the 95 % confidence level. Thus, the search for non-resonant Standard Model hh production sets an observed 95 % confidence level upper limit on the production cross-section \\(\\sigma (pp \\rightarrow hh \\rightarrow b\\bar{b}b\\bar{b})\\) of 202 fb, compared to a Standard Model prediction of \\(\\sigma (pp \\rightarrow hh \\rightarrow b\\bar{b}b\\bar{b}) = 3.6 \\pm 0.5\\) fb.« less

Search for Higgs Boson Pair Production in the γγbb¯ final state using pp collision data at √s = 8 TeV from the ATLAS Detector

DOE PAGES

Aad, G.

2015-02-26

A search for Higgs boson pair production \\(pp \\rightarrow hh\\) is performed with 19.5 fb\\(^{-1}\\) of proton–proton collision data at \\(\\sqrt{s}=8\\) TeV, which were recorded by the ATLAS detector at the Large Hadron Collider in 2012. The decay products of each Higgs boson are reconstructed as a high-momentum \\(b\\bar{b}\\) system with either a pair of small-radius jets or a single large-radius jet, the latter exploiting jet substructure techniques and associated b-tagged track-jets. No evidence for resonant or non-resonant Higgs boson pair production is observed. The data are interpreted in the context of the Randall–Sundrum model with a warped extra dimensionmore » as well as the two-Higgs-doublet model. An upper limit on the cross-section for \\(pp\\rightarrow G^{*}_{\\mathrm {KK}} \\rightarrow hh \\rightarrow b\\bar{b}b\\bar{b} \\) of 3.2 (2.3) fb is set for a Kaluza–Klein graviton \\(G^{*}_{\\mathrm {KK}}\\) mass of 1.0 (1.5) TeV, at the 95 % confidence level. The search for non-resonant Standard Model hh production sets an observed 95 % confidence level upper limit on the production cross-section \\(\\sigma (pp \\rightarrow hh \\rightarrow b\\bar{b}b\\bar{b})\\) of 202 fb, compared to a Standard Model prediction of \\(\\sigma (pp \\rightarrow hh \\rightarrow b\\bar{b}b\\bar{b}) = 3.6 \\pm 0.5\\) fb.« less

Efficacy and Safety of Paliperidone Palmitate 3-Month Formulation for Patients with Schizophrenia: A Randomized, Multicenter, Double-Blind, Noninferiority Study

PubMed Central

Xu, Haiyan; Gopal, Srihari; Nuamah, Isaac; Ravenstijn, Paulien; Janik, Adam; Schotte, Alain; Hough, David; Fleischhacker, Wolfgang W.

2016-01-01

Background: This double-blind, parallel-group, multicenter, phase-3 study was designed to test the noninferiority of paliperidone palmitate 3-month formulation (PP3M) to the currently marketed 1-month formulation (PP1M) in patients (age 18–70 years) with schizophrenia, previously stabilized on PP1M. Methods: After screening (≤3 weeks) and a 17-week, flexible-dosed, open-label phase (PP1M: day 1 [150mg eq. deltoid], day 8 [100mg eq. deltoid.], weeks 5, 9, and 13 [50, 75, 100, or 150mg eq., deltoid/gluteal]), clinically stable patients were randomized (1:1) to PP3M (fixed-dose, 175, 263, 350, or 525mg eq. deltoid/gluteal) or PP1M (fixed-dose, 50, 75, 100, or 150mg eq. deltoid/gluteal) for a 48-week double-blind phase. Results: Overall, 1016/1429 open-label patients entered the double-blind phase (PP3M: n=504; PP1M: n=512) and 842 completed it (including patients with relapse). PP3M was noninferior to PP1M: relapse rates were similar in both groups (PP3M: n=37, 8%; PP1M: n=45, 9%; difference in relapse-free rate: 1.2% [95% CI:-2.7%; 5.1%]) based on Kaplan-Meier estimates (primary efficacy). Secondary endpoint results (changes from double-blind baseline in positive and negative symptom score total and subscale scores, Clinical Global Impression-Severity, and Personal and Social Performance scores) were consistent with primary endpoint results. No clinically relevant differences were observed in pharmacokinetic exposures between PP3M and PP1M. Both groups had similar tolerability profiles; increased weight was the most common treatment-emergent adverse event (double-blind phase; 21% each). No new safety signals were detected. Conclusion: Taken together, PP3M with its 3-month dosing interval is a unique option for relapse prevention in schizophrenia. PMID:26902950

The Zds proteins control entry into mitosis and target protein phosphatase 2A to the Cdc25 phosphatase

PubMed Central

Wicky, Sidonie; Tjandra, Hendri; Schieltz, David; Yates, John; Kellogg, Douglas R.

2011-01-01

The Wee1 kinase restrains entry into mitosis by phosphorylating and inhibiting cyclin-dependent kinase 1 (Cdk1). The Cdc25 phosphatase promotes entry into mitosis by removing Cdk1 inhibitory phosphorylation. Experiments in diverse systems have established that Wee1 and Cdc25 are regulated by protein phosphatase 2A (PP2A), but a full understanding of the function and regulation of PP2A in entry into mitosis has remained elusive. In budding yeast, entry into mitosis is controlled by a specific form of PP2A that is associated with the Cdc55 regulatory subunit (PP2ACdc55). We show here that related proteins called Zds1 and Zds2 form a tight stoichiometric complex with PP2ACdc55 and target its activity to Cdc25 but not to Wee1. Conditional inactivation of the Zds proteins revealed that their function is required primarily at entry into mitosis. In addition, Zds1 undergoes cell cycle–dependent changes in phosphorylation. Together, these observations define a role for the Zds proteins in controlling specific functions of PP2ACdc55 and suggest that upstream signals that regulate PP2ACdc55 may play an important role in controlling entry into mitosis. PMID:21119008

Identification and Characterization of an Alternatively Spliced Isoform of the Human Protein Phosphatase 2Aα Catalytic Subunit*

PubMed Central

Migueleti, Deivid L. S.; Smetana, Juliana H. C.; Nunes, Hugo F.; Kobarg, Jörg; Zanchin, Nilson I. T.

2012-01-01

PP2A is the main serine/threonine-specific phosphatase in animal cells. The active phosphatase has been described as a holoenzyme consisting of a catalytic, a scaffolding, and a variable regulatory subunit, all encoded by multiple genes, allowing for the assembly of more than 70 different holoenzymes. The catalytic subunit can also interact with α4, TIPRL (TIP41, TOR signaling pathway regulator-like), the methyl-transferase LCMT-1, and the methyl-esterase PME-1. Here, we report that the gene encoding the catalytic subunit PP2Acα can generate two mRNA types, the standard mRNA and a shorter isoform, lacking exon 5, which we termed PP2Acα2. Higher levels of the PP2Acα2 mRNA, equivalent to the level of the longer PP2Acα mRNA, were detected in peripheral blood mononuclear cells that were left to rest for 24 h. After this time, the peripheral blood mononuclear cells are still viable and the PP2Acα2 mRNA decreases soon after they are transferred to culture medium, showing that generation of the shorter isoform depends on the incubation conditions. FLAG-tagged PP2Acα2 expressed in HEK293 is catalytically inactive. It displays a specific interaction profile with enhanced binding to the α4 regulatory subunit, but no binding to the scaffolding subunit and PME-1. Consistently, α4 out-competes PME-1 and LCMT-1 for binding to both PP2Acα isoforms in pulldown assays. Together with molecular modeling studies, this suggests that all three regulators share a common binding surface on the catalytic subunit. Our findings add important new insights into the complex mechanisms of PP2A regulation. PMID:22167190

First Observation of the Rare Purely Baryonic Decay B^{0}→pp[over ¯].

PubMed

Aaij, R; Adeva, B; Adinolfi, M; Ajaltouni, Z; Akar, S; Albrecht, J; Alessio, F; Alexander, M; Alfonso Albero, A; Ali, S; Alkhazov, G; Alvarez Cartelle, P; Alves, A A; Amato, S; Amerio, S; Amhis, Y; An, L; Anderlini, L; Andreassi, G; Andreotti, M; Andrews, J E; Appleby, R B; Archilli, F; d'Argent, P; Arnau Romeu, J; Artamonov, A; Artuso, M; Aslanides, E; Auriemma, G; Baalouch, M; Babuschkin, I; Bachmann, S; Back, J J; Badalov, A; Baesso, C; Baker, S; Balagura, V; Baldini, W; Baranov, A; Barlow, R J; Barschel, C; Barsuk, S; Barter, W; Baryshnikov, F; Batozskaya, V; Battista, V; Bay, A; Beaucourt, L; Beddow, J; Bedeschi, F; Bediaga, I; Beiter, A; Bel, L J; Beliy, N; Bellee, V; Belloli, N; Belous, K; Belyaev, I; Ben-Haim, E; Bencivenni, G; Benson, S; Beranek, S; Berezhnoy, A; Bernet, R; Berninghoff, D; Bertholet, E; Bertolin, A; Betancourt, C; Betti, F; Bettler, M-O; van Beuzekom, M; Bezshyiko, Ia; Bifani, S; Billoir, P; Birnkraut, A; Bitadze, A; Bizzeti, A; Bjørn, M; Blake, T; Blanc, F; Blouw, J; Blusk, S; Bocci, V; Boettcher, T; Bondar, A; Bondar, N; Bonivento, W; Bordyuzhin, I; Borgheresi, A; Borghi, S; Borisyak, M; Borsato, M; Bossu, F; Boubdir, M; Bowcock, T J V; Bowen, E; Bozzi, C; Braun, S; Britton, T; Brodzicka, J; Brundu, D; Buchanan, E; Burr, C; Bursche, A; Buytaert, J; Byczynski, W; Cadeddu, S; Cai, H; Calabrese, R; Calladine, R; Calvi, M; Calvo Gomez, M; Camboni, A; Campana, P; Campora Perez, D H; Capriotti, L; Carbone, A; Carboni, G; Cardinale, R; Cardini, A; Carniti, P; Carson, L; Carvalho Akiba, K; Casse, G; Cassina, L; Castillo Garcia, L; Cattaneo, M; Cavallero, G; Cenci, R; Chamont, D; Charles, M; Charpentier, Ph; Chatzikonstantinidis, G; Chefdeville, M; Chen, S; Cheung, S F; Chitic, S-G; Chobanova, V; Chrzaszcz, M; Chubykin, A; Ciambrone, P; Cid Vidal, X; Ciezarek, G; Clarke, P E L; Clemencic, M; Cliff, H V; Closier, J; Cogan, J; Cogneras, E; Cogoni, V; Cojocariu, L; Collins, P; Colombo, T; Comerma-Montells, A; Contu, A; Cook, A; Coombs, G; Coquereau, S; Corti, G; Corvo, M; Costa Sobral, C M; Couturier, B; Cowan, G A; Craik, D C; Crocombe, A; Cruz Torres, M; Currie, R; D'Ambrosio, C; Da Cunha Marinho, F; Dall'Occo, E; Dalseno, J; Davis, A; De Aguiar Francisco, O; De Capua, S; De Cian, M; De Miranda, J M; De Paula, L; De Serio, M; De Simone, P; Dean, C T; Decamp, D; Del Buono, L; Dembinski, H-P; Demmer, M; Dendek, A; Derkach, D; Deschamps, O; Dettori, F; Dey, B; Di Canto, A; Di Nezza, P; Dijkstra, H; Dordei, F; Dorigo, M; Dosil Suárez, A; Douglas, L; Dovbnya, A; Dreimanis, K; Dufour, L; Dujany, G; Durante, P; Dzhelyadin, R; Dziewiecki, M; Dziurda, A; Dzyuba, A; Easo, S; Ebert, M; Egede, U; Egorychev, V; Eidelman, S; Eisenhardt, S; Eitschberger, U; Ekelhof, R; Eklund, L; Ely, S; Esen, S; Evans, H M; Evans, T; Falabella, A; Farley, N; Farry, S; Fazzini, D; Federici, L; Ferguson, D; Fernandez, G; Fernandez Declara, P; Fernandez Prieto, A; Ferrari, F; Ferreira Rodrigues, F; Ferro-Luzzi, M; Filippov, S; Fini, R A; Fiore, M; Fiorini, M; Firlej, M; Fitzpatrick, C; Fiutowski, T; Fleuret, F; Fohl, K; Fontana, M; Fontanelli, F; Forshaw, D C; Forty, R; Franco Lima, V; Frank, M; Frei, C; Fu, J; Funk, W; Furfaro, E; Färber, C; Gabriel, E; Gallas Torreira, A; Galli, D; Gallorini, S; Gambetta, S; Gandelman, M; Gandini, P; Gao, Y; Garcia Martin, L M; García Pardiñas, J; Garra Tico, J; Garrido, L; Garsed, P J; Gascon, D; Gaspar, C; Gavardi, L; Gazzoni, G; Gerick, D; Gersabeck, E; Gersabeck, M; Gershon, T; Ghez, Ph; Gianì, S; Gibson, V; Girard, O G; Giubega, L; Gizdov, K; Gligorov, V V; Golubkov, D; Golutvin, A; Gomes, A; Gorelov, I V; Gotti, C; Govorkova, E; Grabowski, J P; Graciani Diaz, R; Granado Cardoso, L A; Graugés, E; Graverini, E; Graziani, G; Grecu, A; Greim, R; Griffith, P; Grillo, L; Gruber, L; Gruberg Cazon, B R; Grünberg, O; Gushchin, E; Guz, Yu; Gys, T; Göbel, C; Hadavizadeh, T; Hadjivasiliou, C; Haefeli, G; Haen, C; Haines, S C; Hamilton, B; Han, X; Hancock, T H; Hansmann-Menzemer, S; Harnew, N; Harnew, S T; Harrison, J; Hasse, C; Hatch, M; He, J; Hecker, M; Heinicke, K; Heister, A; Hennessy, K; Henrard, P; Henry, L; van Herwijnen, E; Heß, M; Hicheur, A; Hill, D; Hombach, C; Hopchev, P H; Huard, Z C; Hulsbergen, W; Humair, T; Hushchyn, M; Hutchcroft, D; Ibis, P; Idzik, M; Ilten, P; Jacobsson, R; Jalocha, J; Jans, E; Jawahery, A; Jiang, F; John, M; Johnson, D; Jones, C R; Joram, C; Jost, B; Jurik, N; Kandybei, S; Karacson, M; Kariuki, J M; Karodia, S; Kazeev, N; Kecke, M; Kelsey, M; Kenzie, M; Ketel, T; Khairullin, E; Khanji, B; Khurewathanakul, C; Kirn, T; Klaver, S; Klimaszewski, K; Klimkovich, T; Koliiev, S; Kolpin, M; Komarov, I; Kopecna, R; Koppenburg, P; Kosmyntseva, A; Kotriakhova, S; Kozeiha, M; Kravchuk, L; Kreps, M; Krokovny, P; Kruse, F; Krzemien, W; Kucewicz, W; Kucharczyk, M; Kudryavtsev, V; Kuonen, A K; Kurek, K; Kvaratskheliya, T; Lacarrere, D; Lafferty, G; Lai, A; Lanfranchi, G; Langenbruch, C; Latham, T; Lazzeroni, C; Le Gac, R; Leflat, A; Lefrançois, J; Lefèvre, R; Lemaitre, F; Lemos Cid, E; Leroy, O; Lesiak, T; Leverington, B; Li, P-R; Li, T; Li, Y; Li, Z; Likhomanenko, T; Lindner, R; Lionetto, F; Lisovskyi, V; Liu, X; Loh, D; Loi, A; Longstaff, I; Lopes, J H; Lucchesi, D; Lucio Martinez, M; Luo, H; Lupato, A; Luppi, E; Lupton, O; Lusiani, A; Lyu, X; Machefert, F; Maciuc, F; Macko, V; Mackowiak, P; Maddrell-Mander, S; Maev, O; Maguire, K; Maisuzenko, D; Majewski, M W; Malde, S; Malinin, A; Maltsev, T; Manca, G; Mancinelli, G; Manning, P; Marangotto, D; Maratas, J; Marchand, J F; Marconi, U; Marin Benito, C; Marinangeli, M; Marino, P; Marks, J; Martellotti, G; Martin, M; Martinelli, M; Martinez Santos, D; Martinez Vidal, F; Martins Tostes, D; Massacrier, L M; Massafferri, A; Matev, R; Mathad, A; Mathe, Z; Matteuzzi, C; Mauri, A; Maurice, E; Maurin, B; Mazurov, A; McCann, M; McNab, A; McNulty, R; Mead, J V; Meadows, B; Meaux, C; Meier, F; Meinert, N; Melnychuk, D; Merk, M; Merli, A; Michielin, E; Milanes, D A; Millard, E; Minard, M-N; Minzoni, L; Mitzel, D S; Mogini, A; Molina Rodriguez, J; Mombacher, T; Monroy, I A; Monteil, S; Morandin, M; Morello, M J; Morgunova, O; Moron, J; Morris, A B; Mountain, R; Muheim, F; Mulder, M; Müller, D; Müller, J; Müller, K; Müller, V; Naik, P; Nakada, T; Nandakumar, R; Nandi, A; Nasteva, I; Needham, M; Neri, N; Neubert, S; Neufeld, N; Neuner, M; Nguyen, T D; Nguyen-Mau, C; Nieswand, S; Niet, R; Nikitin, N; Nikodem, T; Nogay, A; O'Hanlon, D P; Oblakowska-Mucha, A; Obraztsov, V; Ogilvy, S; Oldeman, R; Onderwater, C J G; Ossowska, A; Otalora Goicochea, J M; Owen, P; Oyanguren, A; Pais, P R; Palano, A; Palutan, M; Papanestis, A; Pappagallo, M; Pappalardo, L L; Parker, W; Parkes, C; Passaleva, G; Pastore, A; Patel, M; Patrignani, C; Pearce, A; Pellegrino, A; Penso, G; Pepe Altarelli, M; Perazzini, S; Perret, P; Pescatore, L; Petridis, K; Petrolini, A; Petrov, A; Petruzzo, M; Picatoste Olloqui, E; Pietrzyk, B; Pikies, M; Pinci, D; Pistone, A; Piucci, A; Placinta, V; Playfer, S; Plo Casasus, M; Polci, F; Poli Lener, M; Poluektov, A; Polyakov, I; Polycarpo, E; Pomery, G J; Ponce, S; Popov, A; Popov, D; Poslavskii, S; Potterat, C; Price, E; Prisciandaro, J; Prouve, C; Pugatch, V; Puig Navarro, A; Pullen, H; Punzi, G; Qian, W; Quagliani, R; Quintana, B; Rachwal, B; Rademacker, J H; Rama, M; Ramos Pernas, M; Rangel, M S; Raniuk, I; Ratnikov, F; Raven, G; Ravonel Salzgeber, M; Reboud, M; Redi, F; Reichert, S; Dos Reis, A C; Remon Alepuz, C; Renaudin, V; Ricciardi, S; Richards, S; Rihl, M; Rinnert, K; Rives Molina, V; Robbe, P; Robert, A; Rodrigues, A B; Rodrigues, E; Rodriguez Lopez, J A; Rodriguez Perez, P; Rogozhnikov, A; Roiser, S; Rollings, A; Romanovskiy, V; Romero Vidal, A; Ronayne, J W; Rotondo, M; Rudolph, M S; Ruf, T; Ruiz Valls, P; Ruiz Vidal, J; Saborido Silva, J J; Sadykhov, E; Sagidova, N; Saitta, B; Salustino Guimaraes, V; Sanchez Mayordomo, C; Sanmartin Sedes, B; Santacesaria, R; Santamarina Rios, C; Santimaria, M; Santovetti, E; Sarpis, G; Sarti, A; Satriano, C; Satta, A; Saunders, D M; Savrina, D; Schael, S; Schellenberg, M; Schiller, M; Schindler, H; Schlupp, M; Schmelling, M; Schmelzer, T; Schmidt, B; Schneider, O; Schopper, A; Schreiner, H F; Schubert, K; Schubiger, M; Schune, M-H; Schwemmer, R; Sciascia, B; Sciubba, A; Semennikov, A; Sepulveda, E S; Sergi, A; Serra, N; Serrano, J; Sestini, L; Seyfert, P; Shapkin, M; Shapoval, I; Shcheglov, Y; Shears, T; Shekhtman, L; Shevchenko, V; Siddi, B G; Silva Coutinho, R; Silva de Oliveira, L; Simi, G; Simone, S; Sirendi, M; Skidmore, N; Skwarnicki, T; Smith, E; Smith, I T; Smith, J; Smith, M; Soares Lavra, L; Sokoloff, M D; Soler, F J P; Souza De Paula, B; Spaan, B; Spradlin, P; Sridharan, S; Stagni, F; Stahl, M; Stahl, S; Stefko, P; Stefkova, S; Steinkamp, O; Stemmle, S; Stenyakin, O; Stepanova, M; Stevens, H; Stone, S; Storaci, B; Stracka, S; Stramaglia, M E; Straticiuc, M; Straumann, U; Sun, J; Sun, L; Sutcliffe, W; Swientek, K; Syropoulos, V; Szczekowski, M; Szumlak, T; Szymanski, M; T'Jampens, S; Tayduganov, A; Tekampe, T; Tellarini, G; Teubert, F; Thomas, E; van Tilburg, J; Tilley, M J; Tisserand, V; Tobin, M; Tolk, S; Tomassetti, L; Tonelli, D; Toriello, F; Tourinho Jadallah Aoude, R; Tournefier, E; Traill, M; Tran, M T; Tresch, M; Trisovic, A; Tsaregorodtsev, A; Tsopelas, P; Tully, A; Tuning, N; Ukleja, A; Usachov, A; Ustyuzhanin, A; Uwer, U; Vacca, C; Vagner, A; Vagnoni, V; Valassi, A; Valat, S; Valenti, G; Vazquez Gomez, R; Vazquez Regueiro, P; Vecchi, S; van Veghel, M; Velthuis, J J; Veltri, M; Veneziano, G; Venkateswaran, A; Verlage, T A; Vernet, M; Vesterinen, M; Viana Barbosa, J V; Viaud, B; Vieira, D; Vieites Diaz, M; Viemann, H; Vilasis-Cardona, X; Vitti, M; Volkov, V; Vollhardt, A; Voneki, B; Vorobyev, A; Vorobyev, V; Voß, C; de Vries, J A; Vázquez Sierra, C; Waldi, R; Wallace, C; Wallace, R; Walsh, J; Wang, J; Ward, D R; Wark, H M; Watson, N K; Websdale, D; Weiden, A; Whitehead, M; Wicht, J; Wilkinson, G; Wilkinson, M; Williams, M; Williams, M P; Williams, M; Williams, T; Wilson, F F; Wimberley, J; Winn, M; Wishahi, J; Wislicki, W; Witek, M; Wormser, G; Wotton, S A; Wraight, K; Wyllie, K; Xie, Y; Xu, Z; Yang, Z; Yang, Z; Yao, Y; Yin, H; Yu, J; Yuan, X; Yushchenko, O; Zarebski, K A; Zavertyaev, M; Zhang, L; Zhang, Y; Zhelezov, A; Zheng, Y; Zhu, X; Zhukov, V; Zonneveld, J B; Zucchelli, S

2017-12-08

The first observation of the decay of a B^{0} meson to a purely baryonic final state, B^{0}→pp[over ¯], is reported. The proton-proton collision data sample used was collected with the LHCb experiment at center-of-mass energies of 7 and 8 TeV and corresponds to an integrated luminosity of 3.0  fb^{-1}. The branching fraction is determined to be B(B^{0}→pp[over ¯])=(1.25±0.27±0.18)×10^{-8}, where the first uncertainty is statistical and the second systematic. The decay mode B^{0}→pp[over ¯] is the rarest decay of the B^{0} meson observed to date. The decay B_{s}^{0}→pp[over ¯] is also investigated. No signal is seen and the upper limit B(B_{s}^{0}→pp[over ¯])<1.5×10^{-8} at 90% confidence level is set on the branching fraction.

Cyclin B Translation Depends on mTOR Activity after Fertilization in Sea Urchin Embryos

PubMed Central

Boulben, Sandrine; Glippa, Virginie; Morales, Julia; Cormier, Patrick

2016-01-01

The cyclin B/CDK1 complex is a key regulator of mitotic entry. Using PP242, a specific ATP-competitive inhibitor of mTOR kinase, we provide evidence that the mTOR signalling pathway controls cyclin B mRNA translation following fertilization in Sphaerechinus granularis and Paracentrotus lividus. We show that PP242 inhibits the degradation of the cap-dependent translation repressor 4E-BP (eukaryotic initiation factor 4E-Binding Protein). PP242 inhibits global protein synthesis, delays cyclin B accumulation, cyclin B/CDK1 complex activation and consequently entry into the mitotic phase of the cell cycle triggered by fertilization. PP242 inhibits cyclin B mRNA recruitment into active polysomes triggered by fertilization. An amount of cyclin B mRNA present in active polysomes appears to be insensitive to PP242 treatment. Taken together, our results suggest that, following sea urchin egg fertilization, cyclin B mRNA translation is controlled by two independent mechanisms: a PP242-sensitive and an additional PP242-insentitive mechanism. PMID:26962866

Testing peak cycling performance: effects of braking force during growth.

PubMed

Doré, E; Bedu, M; França, N M; Diallo, O; Duché, P; Van Praagh, E

2000-02-01

The purpose of this study was to investigate the relationship between cycling peak power (CPP; flywheel inertia included) and the applied braking force (F(B)) on a friction-loaded cycle ergometer in male children, adolescents, and adults. A total of 520 male subjects aged 8-20 yr performed three brief maximal sprints against three F(B): 0.245, 0.491, and 0.736 N x kg(-1) body mass (BM) (corresponding applied loads: 25 [F(B)25], 50 [F(B)50], and 75 [F(B)75] g x kg(-1) BM). For each F(B), peak power (PP) was measured (PP25, PP50 and PP75). For each subject, the highest PP was defined as CPP. Results showed that PP was dependent on F(B). In young adults PP25 underestimated CPP by more than 10%, and consequently, F(B)25 seemed to be too low for this population. However, in children, PP75 underestimated CPP by about 20%. A F(B) of 0.736 N x kg(-1) BM was definitively too high for the pediatric population. Therefore, the optimal F(B), even corrected for BM, was lower in children than in adults. The influence of growth and maturation on the force-generating capacity of the leg muscles may explain this difference. In this study, however, it was shown that the difference between PP50 and CPP was independent of age for the whole population investigated. Consequently, when flywheel inertia is included, one cycling sprint with a F(B) of 0.495 N x kg(-1) BM (corresponding applied load: 50 g x kg(-1) BM) is a feasible method for testing both children, adolescents, or young adults.

Heteroleptic copper(I) complexes prepared from phenanthroline and bis-phosphine ligands.

PubMed

Kaeser, Adrien; Mohankumar, Meera; Mohanraj, John; Monti, Filippo; Holler, Michel; Cid, Juan-José; Moudam, Omar; Nierengarten, Iwona; Karmazin-Brelot, Lydia; Duhayon, Carine; Delavaux-Nicot, Béatrice; Armaroli, Nicola; Nierengarten, Jean-François

2013-10-21

Preparation of [Cu(NN)(PP)](+) derivatives has been systematically investigated starting from two libraries of phenanthroline (NN) derivatives and bis-phosphine (PP) ligands, namely, (A) 1,10-phenanthroline (phen), neocuproine (2,9-dimethyl-1,10-phenanthroline, dmp), bathophenanthroline (4,7-diphenyl-1,10-phenanthroline, Bphen), 2,9-diphenethyl-1,10-phenanthroline (dpep), and 2,9-diphenyl-1,10-phenanthroline (dpp); (B) bis(diphenylphosphino)methane (dppm), 1,2-bis(diphenylphosphino)ethane (dppe), 1,3-bis(diphenylphosphino)propane (dppp), 1,2-bis(diphenylphosphino)benzene (dppb), 1,1'-bis(diphenylphosphino)ferrocene (dppFc), and bis[(2-diphenylphosphino)phenyl] ether (POP). Whatever the bis-phosphine ligand, stable heteroleptic [Cu(NN)(PP)](+) complexes are obtained from the 2,9-unsubstituted-1,10-phenanthroline ligands (phen and Bphen). By contrast, heteroleptic complexes obtained from dmp and dpep are stable in the solid state, but a dynamic ligand exchange reaction is systematically observed in solution, and the homoleptic/heteroleptic ratio is highly dependent on the bis-phosphine ligand. Detailed analysis revealed that the dynamic equilibrium resulting from ligand exchange reactions is mainly influenced by the relative thermodynamic stability of the different possible complexes. Finally, in the case of dpp, only homoleptic complexes were obtained whatever the bis-phosphine ligand. Obviously, steric effects resulting from the presence of the bulky phenyl rings on the dpp ligand destabilize the heteroleptic [Cu(NN)(PP)](+) complexes. In addition to the remarkable thermodynamic stability of [Cu(dpp)2]BF4, this negative steric effect drives the dynamic complexation scenario toward almost exclusive formation of homoleptic [Cu(NN)2](+) and [Cu(PP)2](+) complexes. This work provides the definitive rationalization of the stability of [Cu(NN)(PP)](+) complexes, marking the way for future developments in this field.

Structure-Activity Relationship Studies Using Natural and Synthetic Okadaic Acid/Dinophysistoxin Toxins.

PubMed

Twiner, Michael J; Doucette, Gregory J; Pang, Yucheng; Fang, Chao; Forsyth, Craig J; Miles, Christopher O

2016-11-04

Okadaic acid (OA) and the closely related dinophysistoxins (DTXs) are algal toxins that accumulate in shellfish and are known serine/threonine protein phosphatase (ser/thr PP) inhibitors. Phosphatases are important modulators of enzyme activity and cell signaling pathways. However, the interactions between the OA/DTX toxins and phosphatases are not fully understood. This study sought to identify phosphatase targets and characterize their structure-activity relationships (SAR) with these algal toxins using a combination of phosphatase activity and cytotoxicity assays. Preliminary screening of 21 human and yeast phosphatases indicated that only three ser/thr PPs (PP2a, PP1, PP5) were inhibited by physiologically saturating concentrations of DTX2 (200 nM). SAR studies employed naturally-isolated OA, DTX1, and DTX2, which vary in degree and/or position of methylation, in addition to synthetic 2- epi -DTX2. OA/DTX analogs induced cytotoxicity and inhibited PP activity with a relatively conserved order of potency: OA = DTX1 ≥ DTX2 > 2- epi -DTX. The PPs were also differentially inhibited with sensitivities of PP2a > PP5 > PP1. These findings demonstrate that small variations in OA/DTX toxin structures, particularly at the head region (i.e., C1/C2), result in significant changes in toxicological potency, whereas changes in methylation at C31 and C35 (tail region) only mildly affect potency. In addition to this being the first study to extensively test OA/DTX analogs' activities towards PP5, these data will be helpful for accurately determining toxic equivalence factors (TEFs), facilitating molecular modeling efforts, and developing highly selective phosphatase inhibitors.

Molecular mechanism of serine/threonine protein phosphatase 1 (PP1cα-PP1r7) in spermatogenesis of Toxocara canis.

PubMed

Ma, Guang Xu; Zhou, Rong Qiong; Song, Zhen Hui; Zhu, Hong Hong; Zhou, Zuo Yong; Zeng, Yuan Qin

2015-09-01

Toxocariasis is one of the most important, but neglected, zoonoses, which is mainly caused by Toxocara canis. To better understand the role of serine/threonine protein phosphatase 1 (PP1) in reproductive processes of male adult T. canis, differential expression analysis was used to reveal the profiles of PP1 catalytic subunit α (PP1cα) gene Tc-stp-1 and PP1 regulatory subunit 7 (PP1r7) gene TcM-1309. Indirect fluorescence immunocytochemistry was carried out to determine the subcellular distribution of PP1cα. Double-stranded RNA interference (RNAi) assays were employed to illustrate the function and mechanism of PP1cα in male adult reproduction. Real-time quantitative PCR (qPCR) showed transcriptional consistency of Tc-stp-1 and TcM-1309 in sperm-producing germline tissues and localization research showed cytoplasmic distribution of PP1cα in sf9 cells, which indicated relevant involvements of PP1cα and PP1r7 in spermatogenesis. Moreover, spatiotemporal transcriptional differences of Tc-stp-1 were determined by gene knockdown analysis, which revealed abnormal morphologies and blocked meiotic divisions of spermatocytes by phenotypic aberration scanning, thereby highlighting the crucial involvement of PP1cα in spermatogenesis. These results revealed a PP1cα-PP1r7 mechanism by which PP1 regulates kinetochore-microtubule interactions in spermatogenesis and provided important clues to identify novel drug or vaccine targets for toxocariasis control. Copyright © 2015 Elsevier B.V. All rights reserved.

Crystal structure of a protein phosphatase 2A heterotrimeric holoenzyme.

PubMed

Cho, Uhn Soo; Xu, Wenqing

2007-01-04

Protein phosphatase 2A (PP2A) is a principal Ser/Thr phosphatase, the deregulation of which is associated with multiple human cancers, Alzheimer's disease and increased susceptibility to pathogen infections. How PP2A is structurally organized and functionally regulated remains unclear. Here we report the crystal structure of an AB'C heterotrimeric PP2A holoenzyme. The structure reveals that the HEAT repeats of the scaffold A subunit form a horseshoe-shaped fold, holding the catalytic C and regulatory B' subunits together on the same side. The regulatory B' subunit forms pseudo-HEAT repeats and interacts with the C subunit near the active site, thereby defining substrate specificity. The methylated carboxy-terminal tail of the C subunit interacts with a highly negatively charged region at the interface between A and B' subunits, suggesting that the C-terminal carboxyl methylation of the C subunit promotes B' subunit recruitment by neutralizing charge repulsion. Together, our structural results establish a crucial foundation for understanding PP2A assembly, substrate recruitment and regulation.

Basal protein phosphatase 2A activity restrains cytokine expression: role for MAPKs and tristetraprolin.

PubMed

Rahman, Md Mostafizur; Rumzhum, Nowshin N; Morris, Jonathan C; Clark, Andrew R; Verrills, Nicole M; Ammit, Alaina J

2015-05-18

PP2A is a master controller of multiple inflammatory signaling pathways. It is a target in asthma; however the molecular mechanisms by which PP2A controls inflammation warrant further investigation. In A549 lung epithelial cells in vitro we show that inhibition of basal PP2A activity by okadaic acid (OA) releases restraint on MAPKs and thereby increases MAPK-mediated pro-asthmatic cytokines, including IL-6 and IL-8. Notably, PP2A inhibition also impacts on the anti-inflammatory protein - tristetraprolin (TTP), a destabilizing RNA binding protein regulated at multiple levels by p38 MAPK. Although PP2A inhibition increases TTP mRNA expression, resultant TTP protein builds up in the hyperphosphorylated inactive form. Thus, when PP2A activity is repressed, pro-inflammatory cytokines increase and anti-inflammatory proteins are rendered inactive. Importantly, these effects can be reversed by the PP2A activators FTY720 and AAL(s), or more specifically by overexpression of the PP2A catalytic subunit (PP2A-C). Moreover, PP2A plays an important role in cytokine expression in cells stimulated with TNFα; as inhibition of PP2A with OA or PP2A-C siRNA results in significant increases in cytokine production. Collectively, these data reveal the molecular mechanisms of PP2A regulation and highlight the potential of boosting the power of endogenous phosphatases as novel anti-inflammatory strategies to combat asthmatic inflammation.

Antagonistic activities of the immunomodulator and PP2A-activating drug FTY720 (Fingolimod, Gilenya) in Jak2-driven hematologic malignancies

PubMed Central

Oaks, Joshua J.; Santhanam, Ramasamy; Walker, Christopher J.; Roof, Steve; Harb, Jason G.; Ferenchak, Greg; Eisfeld, Ann-Kathrin; Van Brocklyn, James R.; Briesewitz, Roger; Saddoughi, Sahar A.; Nagata, Kyosuke; Bittman, Robert; Caligiuri, Michael A.; Abdel-Wahab, Omar; Levine, Ross; Arlinghaus, Ralph B.; Quintas-Cardama, Alfonso; Goldman, John M.; Apperley, Jane; Reid, Alistair; Milojkovic, Dragana; Ziolo, Mark T.; Marcucci, Guido; Ogretmen, Besim; Neviani, Paolo

2013-01-01

FTY720 (Fingolimod, Gilenya) is a sphingosine analog used as an immunosuppressant in multiple sclerosis patients. FTY720 is also a potent protein phosphatase 2A (PP2A)–activating drug (PAD). PP2A is a tumor suppressor found inactivated in different types of cancer. We show here that PP2A is inactive in polycythemia vera (PV) and other myeloproliferative neoplasms characterized by the expression of the transforming Jak2V617F oncogene. PP2A inactivation occurs in a Jak2V617F dose/kinase-dependent manner through the PI-3Kγ-PKC–induced phosphorylation of the PP2A inhibitor SET. Genetic or PAD-mediated PP2A reactivation induces Jak2V617F inactivation/downregulation and impairs clonogenic potential of Jak2V617F cell lines and PV but not normal CD34+ progenitors. Likewise, FTY720 decreases leukemic allelic burden, reduces splenomegaly, and significantly increases survival of Jak2V617F leukemic mice without adverse effects. Mechanistically, we show that in Jak2V617F cells, FTY720 antileukemic activity requires neither FTY720 phosphorylation (FTY720-P) nor SET dimerization or ceramide induction but depends on interaction with SET K209. Moreover, we show that Jak2V617F also utilizes an alternative sphingosine kinase-1–mediated pathway to inhibit PP2A and that FTY720-P, acting as a sphingosine-1-phosphate-receptor-1 agonist, elicits signals leading to the Jak2-PI-3Kγ-PKC-SET–mediated PP2A inhibition. Thus, PADs (eg, FTY720) represent suitable therapeutic alternatives for Jak2V617F MPNs. PMID:23926298

The combinatorial PP1-binding consensus Motif (R/K)x( (0,1))V/IxFxx(R/K)x(R/K) is a new apoptotic signature.

PubMed

Godet, Angélique N; Guergnon, Julien; Maire, Virginie; Croset, Amélie; Garcia, Alphonse

2010-04-01

Previous studies established that PP1 is a target for Bcl-2 proteins and an important regulator of apoptosis. The two distinct functional PP1 consensus docking motifs, R/Kx((0,1))V/IxF and FxxR/KxR/K, involved in PP1 binding and cell death were previously characterized in the BH1 and BH3 domains of some Bcl-2 proteins. In this study, we demonstrate that DPT-AIF(1), a peptide containing the AIF(562-571) sequence located in a c-terminal domain of AIF, is a new PP1 interacting and cell penetrating molecule. We also showed that DPT-AIF(1) provoked apoptosis in several human cell lines. Furthermore, DPT-APAF(1) a bi-partite cell penetrating peptide containing APAF-1(122-131), a non penetrating sequence from APAF-1 protein, linked to our previously described DPT-sh1 peptide shuttle, is also a PP1-interacting death molecule. Both AIF(562-571) and APAF-1(122-131) sequences contain a common R/Kx((0,1))V/IxFxxR/KxR/K motif, shared by several proteins involved in control of cell survival pathways. This motif combines the two distinct PP1c consensus docking motifs initially identified in some Bcl-2 proteins. Interestingly DPT-AIF(2) and DPT-APAF(2) that carry a F to A mutation within this combinatorial motif, no longer exhibited any PP1c binding or apoptotic effects. Moreover the F to A mutation in DPT-AIF(2) also suppressed cell penetration. These results indicate that the combinatorial PP1c docking motif R/Kx((0,1))V/IxFxxR/KxR/K, deduced from AIF(562-571) and APAF-1(122-131) sequences, is a new PP1c-dependent Apoptotic Signature. This motif is also a new tool for drug design that could be used to characterize potential anti-tumour molecules.

Homemade-device-induced negative pressure promotes wound healing more efficiently than VSD-induced positive pressure by regulating inflammation, proliferation and remodeling

PubMed Central

Liu, Jinyan; Hu, Feng; Tang, Jintian; Tang, Shijie; Xia, Kun; Wu, Song; Yin, Chaoqi; Wang, Shaohua; He, Quanyong; Xie, Huiqing; Zhou, Jianda

2017-01-01

Vacuum sealing drainage (VSD) is an effective technique used to promote wound healing. However, recent studies have shown that it exerts positive pressure (PP) rather than negative pressure (NP) on skin. In this study, we created a homemade device that could maintain NP on the wound, and compared the therapeutic effects of VSD-induced PP to those of our home-made device which induced NP on wound healing. The NP induced by our device required less time for wound healing and decreased the wound area more efficiently than the PP induced by VSD. NP and PP both promoted the inflammatory response by upregulating neutrophil infiltration and interleukin (IL)-1β expression, and downregulating IL-10 expression. Higher levels of epidermal growth factor (EGF), transforming growth factor (TGF)-β and platelet-derived growth factor (PDGF), and lower levels of basic fibroblast growth factor (bFGF) were observed in the wound tissue treated with NP compared to the wound tissue exposed to PP. Proliferation in the wound tissue exposed to NP on day 10 was significantly higher than that in wound tissue exposed to PP. NP generated more fibroblasts, keratinized stratified epithelium, and less epithelia with stemness than PP. The levels of ccollagen I and III were both decreased in both the NP and PP groups. NP induced a statistically significant increase in the expression of fibronectin (FN) on days 3 and 10 compared to PP. Furthermore, the level of matrix metalloproteinase (MMP)-13 increased in the NP group, but decreased in the PP group on day 3. NP also induced a decrease in the levels of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 during the early stages of wound healing, which was significantly different from the increasing effect of PP on TIMP-1 and TIMP-2 levels at the corresponding time points. On the whole, our data indicate that our homemade device which induced NP, was more efficient than VSD-induced PP on wound healing by regulating inflammation, secretion, proliferation and the distribution of different cells in wound tissue. PMID:28290607

An Enterotoxin-Like Binary Protein from Pseudomonas protegens with Potent Nematicidal Activity.

PubMed

Wei, Jun-Zhi; Siehl, Daniel L; Hou, Zhenglin; Rosen, Barbara; Oral, Jarred; Taylor, Christopher G; Wu, Gusui

2017-10-01

Soil microbes are a major food source for free-living soil nematodes. It is known that certain soil bacteria have evolved systems to combat predation. We identified the nematode-antagonistic Pseudomonas protegens strain 15G2 from screening of microbes. Through protein purification we identified a binary protein, designated Pp-ANP, which is responsible for the nematicidal activity. This binary protein inhibits Caenorhabditis elegans growth and development by arresting larvae at the L1 stage and killing older-staged worms. The two subunits, Pp-ANP1a and Pp-ANP2a, are active when reconstituted from separate expression in Escherichia coli The binary toxin also shows strong nematicidal activity against three other free-living nematodes ( Pristionchus pacificus , Panagrellus redivivus , and Acrobeloides sp.), but we did not find any activity against insects and fungi under test conditions, indicating specificity for nematodes. Pp-ANP1a has no significant identity to any known proteins, while Pp-ANP2a shows ∼30% identity to E. coli heat-labile enterotoxin (LT) subunit A and cholera toxin (CT) subunit A. Protein modeling indicates that Pp-ANP2a is structurally similar to CT/LT and likely acts as an ADP-ribosyltransferase. Despite the similarity, Pp-ANP shows several characteristics distinct from CT/LT toxins. Our results indicate that Pp-ANP is a new enterotoxin-like binary toxin with potent and specific activity to nematodes. The potency and specificity of Pp-ANP suggest applications in controlling parasitic nematodes and open an avenue for further research on its mechanism of action and role in bacterium-nematode interaction. IMPORTANCE This study reports the discovery of a new enterotoxin-like binary protein, Pp-ANP, from a Pseudomonas protegens strain. Pp-ANP shows strong nematicidal activity against Caenorhabditis elegans larvae and older-staged worms. It also shows strong activity on other free-living nematodes ( Pristionchus pacificus , Panagrellus redivivus , and Acrobeloides sp.). The two subunits, Pp-ANP1a and Pp-ANP2a, can be expressed separately and reconstituted to form the active complex. Pp-ANP shows some distinct characteristics compared with other toxins, including Escherichia coli enterotoxin and cholera toxin. The present study indicates that Pp-ANP is a novel binary toxin and that it has potential applications in controlling parasitic nematodes and in studying toxin-host interaction. Copyright © 2017 Wei et al.

Expression of peach sucrose transporters in heterologous systems points out their different physiological role.

PubMed

Zanon, Laura; Falchi, Rachele; Hackel, Aleksandra; Kühn, Christina; Vizzotto, Giannina

2015-09-01

Sucrose is the major phloem-translocated component in a number of economically important plant species. The comprehension of the mechanisms involved in sucrose transport in peach fruit appears particularly relevant, since the accumulation of this sugar, during ripening, is crucial for the growth and quality of the fruit. Here, we report the functional characterisation and subcellular localisation of three sucrose transporters (PpSUT1, PpSUT2, PpSUT4) in peach, and we formulate novel hypotheses about their role in accumulation of sugar. We provide evidence, about the capability of both PpSUT1 and PpSUT4, expressed in mutant yeast strains to transport sucrose. The functionality of PpSUT1 at the plasma membrane, and of PpSUT4 at the tonoplast, has been demonstrated. On the other hand, the functionality of PpSUT2 was not confirmed: this protein is unable to complement two sucrose uptake-deficient mutant yeast strains. Our results corroborate the hypotheses that PpSUT1 partakes in phloem loading in leaves, and PpSUT4 sustains cell metabolism by regulating sucrose efflux from the vacuole. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Search for the standard model higgs Boson in the ZH-->nunubb channel in 5.2 fb{-1} of pp collisions at sqrt[s]=1.96 TeV.

PubMed

Abazov, V M; Abbott, B; Abolins, M; Acharya, B S; Adams, M; Adams, T; Aguilo, E; Alexeev, G D; Alkhazov, G; Alton, A; Alverson, G; Alves, G A; Ancu, L S; Aoki, M; Arnoud, Y; Arov, M; Askew, A; Asman, B; Atramentov, O; Avila, C; Backusmayes, J; Badaud, F; Bagby, L; Baldin, B; Bandurin, D V; Banerjee, S; Barberis, E; Barfuss, A-F; Baringer, P; Barreto, J; Bartlett, J F; Bassler, U; Bauer, D; Beale, S; Bean, A; Begalli, M; Begel, M; Belanger-Champagne, C; Bellantoni, L; Benitez, J A; Beri, S B; Bernardi, G; Bernhard, R; Bertram, I; Besançon, M; Beuselinck, R; Bezzubov, V A; Bhat, P C; Bhatnagar, V; Blazey, G; Blessing, S; Bloom, K; Boehnlein, A; Boline, D; Bolton, T A; Boos, E E; Borissov, G; Bose, T; Brandt, A; Brock, R; Brooijmans, G; Bross, A; Brown, D; Bu, X B; Buchholz, D; Buehler, M; Buescher, V; Bunichev, V; Burdin, S; Burnett, T H; Buszello, C P; Calfayan, P; Calpas, B; Calvet, S; Camacho-Pérez, E; Cammin, J; Carrasco-Lizarraga, M A; Carrera, E; Casey, B C K; Castilla-Valdez, H; Chakrabarti, S; Chakraborty, D; Chan, K M; Chandra, A; Cheu, E; Chevalier-Théry, S; Cho, D K; Cho, S W; Choi, S; Choudhary, B; Christoudias, T; Cihangir, S; Claes, D; Clutter, J; Cooke, M; Cooper, W E; Corcoran, M; Couderc, F; Cousinou, M-C; Cutts, D; Cwiok, M; Das, A; Davies, G; De, K; de Jong, S J; De La Cruz-Burelo, E; Devaughan, K; Déliot, F; Demarteau, M; Demina, R; Denisov, D; Denisov, S P; Desai, S; Diehl, H T; Diesburg, M; Dominguez, A; Dorland, T; Dubey, A; Dudko, L V; Duflot, L; Duggan, D; Duperrin, A; Dutt, S; Dyshkant, A; Eads, M; Edmunds, D; Ellison, J; Elvira, V D; Enari, Y; Eno, S; Evans, H; Evdokimov, A; Evdokimov, V N; Facini, G; Ferapontov, A V; Ferbel, T; Fiedler, F; Filthaut, F; Fisher, W; Fisk, H E; Fortner, M; Fox, H; Fuess, S; Gadfort, T; Galea, C F; Garcia-Bellido, A; Gavrilov, V; Gay, P; Geist, W; Geng, W; Gerbaudo, D; Gerber, C E; Gershtein, Y; Gillberg, D; Ginther, G; Golovanov, G; Gómez, B; Goussiou, A; Grannis, P D; Greder, S; Greenlee, H; Greenwood, Z D; Gregores, E M; Grenier, G; Gris, Ph; Grivaz, J-F; Grohsjean, A; Grünendahl, S; Grünewald, M W; Guo, F; Guo, J; Gutierrez, G; Gutierrez, P; Haas, A; Haefner, P; Hagopian, S; Haley, J; Hall, I; Han, L; Harder, K; Harel, A; Hauptman, J M; Hays, J; Hebbeker, T; Hedin, D; Hegeman, J G; Heinson, A P; Heintz, U; Hensel, C; Heredia-De La Cruz, I; Herner, K; Hesketh, G; Hildreth, M D; Hirosky, R; Hoang, T; Hobbs, J D; Hoeneisen, B; Hohlfeld, M; Hossain, S; Houben, P; Hu, Y; Hubacek, Z; Huske, N; Hynek, V; Iashvili, I; Illingworth, R; Ito, A S; Jabeen, S; Jaffré, M; Jain, S; Jamin, D; Jesik, R; Johns, K; Johnson, C; Johnson, M; Johnston, D; Jonckheere, A; Jonsson, P; Juste, A; Kajfasz, E; Karmanov, D; Kasper, P A; Katsanos, I; Kaushik, V; Kehoe, R; Kermiche, S; Khalatyan, N; Khanov, A; Kharchilava, A; Kharzheev, Y N; Khatidze, D; Kirby, M H; Kirsch, M; Kohli, J M; Kozelov, A V; Kraus, J; Kumar, A; Kupco, A; Kurca, T; Kuzmin, V A; Kvita, J; Lam, D; Lammers, S; Landsberg, G; Lebrun, P; Lee, H S; Lee, W M; Leflat, A; Lellouch, J; Li, L; Li, Q Z; Lietti, S M; Lim, J K; Lincoln, D; Linnemann, J; Lipaev, V V; Lipton, R; Liu, Y; Liu, Z; Lobodenko, A; Lokajicek, M; Love, P; Lubatti, H J; Luna-Garcia, R; Lyon, A L; Maciel, A K A; Mackin, D; Mättig, P; Magaña-Villalba, R; Mal, P K; Malik, S; Malyshev, V L; Maravin, Y; Martínez-Ortega, J; McCarthy, R; McGivern, C L; Meijer, M M; Melnitchouk, A; Mendoza, L; Menezes, D; Mercadante, P G; Merkin, M; Meyer, A; Meyer, J; Mommsen, R K; Mondal, N K; Moulik, T; Muanza, G S; Mulhearn, M; Mundal, O; Mundim, L; Nagy, E; Naimuddin, M; Narain, M; Nayyar, R; Neal, H A; Negret, J P; Neustroev, P; Nilsen, H; Nogima, H; Novaes, S F; Nunnemann, T; Obrant, G; Ochando, C; Onoprienko, D; Orduna, J; Osman, N; Osta, J; Otec, R; Otero Y Garzón, G J; Owen, M; Padilla, M; Padley, P; Pangilinan, M; Parashar, N; Parihar, V; Park, S-J; Park, S K; Parsons, J; Partridge, R; Parua, N; Patwa, A; Penning, B; Perfilov, M; Peters, K; Peters, Y; Pétroff, P; Piegaia, R; Piper, J; Pleier, M-A; Podesta-Lerma, P L M; Podstavkov, V M; Pol, M-E; Polozov, P; Popov, A V; Prewitt, M; Price, D; Protopopescu, S; Qian, J; Quadt, A; Quinn, B; Rangel, M S; Ranjan, K; Ratoff, P N; Razumov, I; Renkel, P; Rich, P; Rijssenbeek, M; Ripp-Baudot, I; Rizatdinova, F; Robinson, S; Rominsky, M; Royon, C; Rubinov, P; Ruchti, R; Safronov, G; Sajot, G; Sánchez-Hernández, A; Sanders, M P; Sanghi, B; Savage, G; Sawyer, L; Scanlon, T; Schaile, D; Schamberger, R D; Scheglov, Y; Schellman, H; Schliephake, T; Schlobohm, S; Schwanenberger, C; Schwienhorst, R; Sekaric, J; Severini, H; Shabalina, E; Shary, V; Shchukin, A A; Shivpuri, R K; Simak, V; Sirotenko, V; Skubic, P; Slattery, P; Smirnov, D; Snow, G R; Snow, J; Snyder, S; Söldner-Rembold, S; Sonnenschein, L; Sopczak, A; Sosebee, M; Soustruznik, K; Spurlock, B; Stark, J; Stolin, V; Stoyanova, D A; Strandberg, J; Strang, M A; Strauss, E; Strauss, M; Ströhmer, R; Strom, D; Stutte, L; Svoisky, P; Takahashi, M; Tanasijczuk, A; Taylor, W; Tiller, B; Titov, M; Tokmenin, V V; Tsybychev, D; Tuchming, B; Tully, C; Tuts, P M; Unalan, R; Uvarov, L; Uvarov, S; Uzunyan, S; van den Berg, P J; Van Kooten, R; van Leeuwen, W M; Varelas, N; Varnes, E W; Vasilyev, I A; Verdier, P; Vertogradov, L S; Verzocchi, M; Vesterinen, M; Vilanova, D; Vint, P; Vokac, P; Wahl, H D; Wang, M H L S; Warchol, J; Watts, G; Wayne, M; Weber, G; Weber, M; Wetstein, M; White, A; Wicke, D; Williams, M R J; Wilson, G W; Wimpenny, S J; Wobisch, M; Wood, D R; Wyatt, T R; Xie, Y; Xu, C; Yacoob, S; Yamada, R; Yang, W-C; Yasuda, T; Yatsunenko, Y A; Ye, Z; Yin, H; Yip, K; Yoo, H D; Youn, S W; Yu, J; Zeitnitz, C; Zelitch, S; Zhao, T; Zhou, B; Zhu, J; Zielinski, M; Zieminska, D; Zivkovic, L; Zutshi, V; Zverev, E G

2010-02-19

A search is performed for the standard model Higgs boson in 5.2 fb{-1} of pp collisions at sqrt[s]=1.96 TeV, collected with the D0 detector at the Fermilab Tevatron Collider. The final state considered is a pair of b jets and large missing transverse energy, as expected from pp-->ZH-->nunubb production. The search is also sensitive to the WH-->lnubb channel when the charged lepton is not identified. For a Higgs boson mass of 115 GeV, a limit is set at the 95% C.L. on the cross section multiplied by branching fraction for [pp-->(Z/W)H](H-->bb) that is a factor of 3.7 larger than the standard model value, consistent with the factor of 4.6 expected.

Micro-phytoplankton photosynthesis, primary production and potential export production in the Atlantic Ocean

NASA Astrophysics Data System (ADS)

Tilstone, Gavin H.; Lange, Priscila K.; Misra, Ankita; Brewin, Robert J. W.; Cain, Terry

2017-11-01

Micro-phytoplankton is the >20 μm component of the phytoplankton community and plays a major role in the global ocean carbon pump, through the sequestering of anthropogenic CO2 and export of organic carbon to the deep ocean. To evaluate the global impact of the marine carbon cycle, quantification of micro-phytoplankton primary production is paramount. In this paper we use both in situ data and a satellite model to estimate the contribution of micro-phytoplankton to total primary production (PP) in the Atlantic Ocean. From 1995 to 2013, 940 measurements of primary production were made at 258 sites on 23 Atlantic Meridional Transect Cruises from the United Kingdom to the South African or Patagonian Shelf. Micro-phytoplankton primary production was highest in the South Subtropical Convergence (SSTC ∼ 409 ± 720 mg C m-2 d-1), where it contributed between 38 % of the total PP, and was lowest in the North Atlantic Gyre province (NATL ∼ 37 ± 27 mg C m-2 d-1), where it represented 18 % of the total PP. Size-fractionated photosynthesis-irradiance (PE) parameters measured on AMT22 and 23 showed that micro-phytoplankton had the highest maximum photosynthetic rate (PmB) (∼5 mg C (mg Chl a)-1 h-1) followed by nano- (∼4 mg C (mg Chl a)-1 h-1) and pico- (∼2 mg C (mg Chl a)-1 h-1). The highest PmB was recorded in the NATL and lowest in the North Atlantic Drift Region (NADR) and South Atlantic Gyre (SATL). The PE parameters were used to parameterise a remote sensing model of size-fractionated PP, which explained 84 % of the micro-phytoplankton in situ PP variability with a regression slope close to 1. The model was applied to the SeaWiFS time series from 1998-2010, which illustrated that micro-phytoplankton PP remained constant in the NADR, NATL, Canary Current Coastal upwelling (CNRY), Eastern Tropical Atlantic (ETRA), Western Tropical Atlantic (WTRA) and SATL, but showed a gradual increase in the Benguela Upwelling zone (BENG) and South Subtropical Convergence (SSTC). The mean annual carbon fixation of micro-phytoplankton was highest in the CNRY (∼140 g C m-2 yr-1), and lowest in the SATL (27 g C m-2 yr-1). A Thorium-234 based export production (ThExP) algorithm was applied to estimates of total PP in each province. There was a strong coupling between micro-phytoplankton PP and ThExP in the NADR and SSTC where between 23 and 39 % of micro-phytoplankton PP contributed to ThExP. The lowest contribution by micro-phytoplankton to ThExP was in the ETRA and WTRA which were 15 and 21 % respectively. The results suggest that micro-phytoplankton PP in the SSTC is the most efficient export system and the ETRA is the least efficient in the Atlantic Ocean.

[Preparation and activity validation of PP7 bacteriophage-like particles displaying PAP114-128 peptide].

PubMed

Sun, Yanli; Sun, Yanhua

2016-10-01

Objective To obtain the PP7 bacteriophage-like particles carrying the peptide of prostatic acid phosphatase PAP 114-128 , and prove that they retain the original biological activity. Methods First, the plasmid pETDuet-2PP7 was constructed as follows: the gene of PP7 coat protein dimer was amplified by gene mutation combined with overlapping PCR technology, and inserted into the vector pETDuet-1. Following that, the plasmid pETDuet-2PP7-PAP 114-128 was constructed as follows: the PP7 coat protein gene carrying the coding gene of PAP 114-128 peptide was amplified using PCR, and then inserted into the vector pETDuet-2PP7. Both pETDuet-2PP7 and pETDuet-2PP7-PAP 114-128 were transformed into E.coli and expressed. The expression product was verified by SDS-PAGE, double immunodiffusion assay and ELISA. Results The gene fragment of PP7 coat protein dimer was obtained by overlapping PCR using Ex Taq DNA polymerase, and the antigenicity of its expression product was the same as that of the coat protein of wild-type PP7 bacteriophage. Moreover, the PAP 114-128 peptide epitope that was displayed on the surface of PP7 bacteriophage was identical with the corresponding epitope of natural human PAP, and it was able to induce high levels of antibodies. Conclusion The gene of PP7 coat protein dimer with repeated sequences can be prepared by gene mutation combined with overlapping PCR. Based on this, PP7 bacteriophage-like particles carrying PAP peptide can be prepared, which not only solves the problem of the instability of the peptides, but also lays a foundation for the study on their delivery and function.

Protein phosphatase 2A mediates resensitization of the neurokinin 1 receptor

PubMed Central

Murphy, Jane E.; Roosterman, Dirk; Cottrell, Graeme S.; Padilla, Benjamin E.; Feld, Micha; Brand, Eva; Cedron, Wendy J.; Steinhoff, Martin

2011-01-01

Activated G protein-coupled receptors (GPCRs) are phosphorylated and interact with β-arrestins, which mediate desensitization and endocytosis. Endothelin-converting enzyme-1 (ECE-1) degrades neuropeptides in endosomes and can promote recycling. Although endocytosis, dephosphorylation, and recycling are accepted mechanisms of receptor resensitization, a large proportion of desensitized receptors can remain at the cell surface. We investigated whether reactivation of noninternalized, desensitized (phosphorylated) receptors mediates resensitization of the substance P (SP) neurokinin 1 receptor (NK1R). Herein, we report a novel mechanism of resensitization by which protein phosphatase 2A (PP2A) is recruited to dephosphorylate noninternalized NK1R. A desensitizing concentration of SP reduced cell-surface SP binding sites by only 25%, and SP-induced Ca2+ signals were fully resensitized before cell-surface binding sites started to recover, suggesting resensitization of cell-surface-retained NK1R. SP induced association of β-arrestin1 and PP2A with noninternalized NK1R. β-Arrestin1 small interfering RNA knockdown prevented SP-induced association of cell-surface NK1R with PP2A, indicating that β-arrestin1 mediates this interaction. ECE-1 inhibition, by trapping β-arrestin1 in endosomes, also impeded SP-induced association of cell-surface NK1R with PP2A. Resensitization of NK1R signaling required both PP2A and ECE-1 activity. Thus, after stimulation with SP, PP2A interacts with noninternalized NK1R and mediates resensitization. PP2A interaction with NK1R requires β-arrestin1. ECE-1 promotes this process by releasing β-arrestin1 from NK1R in endosomes. These findings represent a novel mechanism of PP2A- and ECE-1-dependent resensitization of GPCRs. PMID:21795521

First Observation of a Baryonic Bc+ Decay

NASA Astrophysics Data System (ADS)

Aaij, R.; Adeva, B.; Adinolfi, M.; Affolder, A.; Ajaltouni, Z.; Akar, S.; Albrecht, J.; Alessio, F.; Alexander, M.; Ali, S.; Alkhazov, G.; Alvarez Cartelle, P.; Alves, A. A.; Amato, S.; Amerio, S.; Amhis, Y.; An, L.; Anderlini, L.; Anderson, J.; Andreassen, R.; Andreotti, M.; Andrews, J. E.; Appleby, R. B.; Aquines Gutierrez, O.; Archilli, F.; Artamonov, A.; Artuso, M.; Aslanides, E.; Auriemma, G.; Baalouch, M.; Bachmann, S.; Back, J. J.; Badalov, A.; Baldini, W.; Barlow, R. J.; Barschel, C.; Barsuk, S.; Barter, W.; Batozskaya, V.; Battista, V.; Bay, A.; Beaucourt, L.; Beddow, J.; Bedeschi, F.; Bediaga, I.; Belogurov, S.; Belous, K.; Belyaev, I.; Ben-Haim, E.; Bencivenni, G.; Benson, S.; Benton, J.; Berezhnoy, A.; Bernet, R.; Bettler, M.-O.; van Beuzekom, M.; Bien, A.; Bifani, S.; Bird, T.; Bizzeti, A.; Bjørnstad, P. M.; Blake, T.; Blanc, F.; Blouw, J.; Blusk, S.; Bocci, V.; Bondar, A.; Bondar, N.; Bonivento, W.; Borghi, S.; Borgia, A.; Borsato, M.; Bowcock, T. J. V.; Bowen, E.; Bozzi, C.; Brambach, T.; van den Brand, J.; Bressieux, J.; Brett, D.; Britsch, M.; Britton, T.; Brodzicka, J.; Brook, N. H.; Brown, H.; Bursche, A.; Busetto, G.; Buytaert, J.; Cadeddu, S.; Calabrese, R.; Calvi, M.; Calvo Gomez, M.; Campana, P.; Campora Perez, D.; Carbone, A.; Carboni, G.; Cardinale, R.; Cardini, A.; Carson, L.; Carvalho Akiba, K.; Casse, G.; Cassina, L.; Castillo Garcia, L.; Cattaneo, M.; Cauet, Ch.; Cenci, R.; Charles, M.; Charpentier, Ph.; Chefdeville, M.; Chen, S.; Cheung, S.-F.; Chiapolini, N.; Chrzaszcz, M.; Ciba, K.; Cid Vidal, X.; Ciezarek, G.; Clarke, P. E. L.; Clemencic, M.; Cliff, H. V.; Closier, J.; Coco, V.; Cogan, J.; Cogneras, E.; Cojocariu, L.; Collins, P.; Comerma-Montells, A.; Contu, A.; Cook, A.; Coombes, M.; Coquereau, S.; Corti, G.; Corvo, M.; Counts, I.; Couturier, B.; Cowan, G. A.; Craik, D. C.; Cruz Torres, M.; Cunliffe, S.; Currie, R.; D'Ambrosio, C.; Dalseno, J.; David, P.; David, P. N. Y.; Davis, A.; De Bruyn, K.; De Capua, S.; De Cian, M.; De Miranda, J. M.; De Paula, L.; De Silva, W.; De Simone, P.; Decamp, D.; Deckenhoff, M.; Del Buono, L.; Déléage, N.; Derkach, D.; Deschamps, O.; Dettori, F.; Di Canto, A.; Dijkstra, H.; Donleavy, S.; Dordei, F.; Dorigo, M.; Dosil Suárez, A.; Dossett, D.; Dovbnya, A.; Dreimanis, K.; Dujany, G.; Dupertuis, F.; Durante, P.; Dzhelyadin, R.; Dziurda, A.; Dzyuba, A.; Easo, S.; Egede, U.; Egorychev, V.; Eidelman, S.; Eisenhardt, S.; Eitschberger, U.; Ekelhof, R.; Eklund, L.; El Rifai, I.; Elsasser, Ch.; Ely, S.; Esen, S.; Evans, H.-M.; Evans, T.; Falabella, A.; Färber, C.; Farinelli, C.; Farley, N.; Farry, S.; Fay, RF; Ferguson, D.; Fernandez Albor, V.; Ferreira Rodrigues, F.; Ferro-Luzzi, M.; Filippov, S.; Fiore, M.; Fiorini, M.; Firlej, M.; Fitzpatrick, C.; Fiutowski, T.; Fontana, M.; Fontanelli, F.; Forty, R.; Francisco, O.; Frank, M.; Frei, C.; Frosini, M.; Fu, J.; Furfaro, E.; Gallas Torreira, A.; Galli, D.; Gallorini, S.; Gambetta, S.; Gandelman, M.; Gandini, P.; Gao, Y.; García Pardiñas, J.; Garofoli, J.; Garra Tico, J.; Garrido, L.; Gaspar, C.; Gauld, R.; Gavardi, L.; Gavrilov, G.; Geraci, A.; Gersabeck, E.; Gersabeck, M.; Gershon, T.; Ghez, Ph.; Gianelle, A.; Giani', S.; Gibson, V.; Giubega, L.; Gligorov, V. V.; Göbel, C.; Golubkov, D.; Golutvin, A.; Gomes, A.; Gotti, C.; Grabalosa Gándara, M.; Graciani Diaz, R.; Granado Cardoso, L. A.; Graugés, E.; Graziani, G.; Grecu, A.; Greening, E.; Gregson, S.; Griffith, P.; Grillo, L.; Grünberg, O.; Gui, B.; Gushchin, E.; Guz, Yu.; Gys, T.; Hadjivasiliou, C.; Haefeli, G.; Haen, C.; Haines, S. C.; Hall, S.; Hamilton, B.; Hampson, T.; Han, X.; Hansmann-Menzemer, S.; Harnew, N.; Harnew, S. T.; Harrison, J.; He, J.; Head, T.; Heijne, V.; Hennessy, K.; Henrard, P.; Henry, L.; Hernando Morata, J. A.; van Herwijnen, E.; Heß, M.; Hicheur, A.; Hill, D.; Hoballah, M.; Hombach, C.; Hulsbergen, W.; Hunt, P.; Hussain, N.; Hutchcroft, D.; Hynds, D.; Idzik, M.; Ilten, P.; Jacobsson, R.; Jaeger, A.; Jalocha, J.; Jans, E.; Jaton, P.; Jawahery, A.; Jing, F.; John, M.; Johnson, D.; Jones, C. R.; Joram, C.; Jost, B.; Jurik, N.; Kaballo, M.; Kandybei, S.; Kanso, W.; Karacson, M.; Karbach, T. M.; Karodia, S.; Kelsey, M.; Kenyon, I. R.; Ketel, T.; Khanji, B.; Khurewathanakul, C.; Klaver, S.; Klimaszewski, K.; Kochebina, O.; Kolpin, M.; Komarov, I.; Koopman, R. F.; Koppenburg, P.; Korolev, M.; Kozlinskiy, A.; Kravchuk, L.; Kreplin, K.; Kreps, M.; Krocker, G.; Krokovny, P.; Kruse, F.; Kucewicz, W.; Kucharczyk, M.; Kudryavtsev, V.; Kurek, K.; Kvaratskheliya, T.; La Thi, V. N.; Lacarrere, D.; Lafferty, G.; Lai, A.; Lambert, D.; Lambert, R. W.; Lanfranchi, G.; Langenbruch, C.; Langhans, B.; Latham, T.; Lazzeroni, C.; Le Gac, R.; van Leerdam, J.; Lees, J.-P.; Lefèvre, R.; Leflat, A.; Lefrançois, J.; Leo, S.; Leroy, O.; Lesiak, T.; Leverington, B.; Li, Y.; Likhomanenko, T.; Liles, M.; Lindner, R.; Linn, C.; Lionetto, F.; Liu, B.; Lohn, S.; Longstaff, I.; Lopes, J. H.; Lopez-March, N.; Lowdon, P.; Lu, H.; Lucchesi, D.; Luo, H.; Lupato, A.; Luppi, E.; Lupton, O.; Machefert, F.; Machikhiliyan, I. V.; Maciuc, F.; Maev, O.; Malde, S.; Malinin, A.; Manca, G.; Mancinelli, G.; Maratas, J.; Marchand, J. F.; Marconi, U.; Marin Benito, C.; Marino, P.; Märki, R.; Marks, J.; Martellotti, G.; Martens, A.; Martín Sánchez, A.; Martinelli, M.; Martinez Santos, D.; Martinez Vidal, F.; Martins Tostes, D.; Massafferri, A.; Matev, R.; Mathe, Z.; Matteuzzi, C.; Mazurov, A.; McCann, M.; McCarthy, J.; McNab, A.; McNulty, R.; McSkelly, B.; Meadows, B.; Meier, F.; Meissner, M.; Merk, M.; Milanes, D. A.; Minard, M.-N.; Moggi, N.; Molina Rodriguez, J.; Monteil, S.; Morandin, M.; Morawski, P.; Mordà, A.; Morello, M. J.; Moron, J.; Morris, A.-B.; Mountain, R.; Muheim, F.; Müller, K.; Mussini, M.; Muster, B.; Naik, P.; Nakada, T.; Nandakumar, R.; Nasteva, I.; Needham, M.; Neri, N.; Neubert, S.; Neufeld, N.; Neuner, M.; Nguyen, A. D.; Nguyen, T. D.; Nguyen-Mau, C.; Nicol, M.; Niess, V.; Niet, R.; Nikitin, N.; Nikodem, T.; Novoselov, A.; O'Hanlon, D. P.; Oblakowska-Mucha, A.; Obraztsov, V.; Oggero, S.; Ogilvy, S.; Okhrimenko, O.; Oldeman, R.; Onderwater, G.; Orlandea, M.; Otalora Goicochea, J. M.; Owen, P.; Oyanguren, A.; Pal, B. K.; Palano, A.; Palombo, F.; Palutan, M.; Panman, J.; Papanestis, A.; Pappagallo, M.; Pappalardo, L. L.; Parkes, C.; Parkinson, C. J.; Passaleva, G.; Patel, G. D.; Patel, M.; Patrignani, C.; Pazos Alvarez, A.; Pearce, A.; Pellegrino, A.; Pepe Altarelli, M.; Perazzini, S.; Perez Trigo, E.; Perret, P.; Perrin-Terrin, M.; Pescatore, L.; Pesen, E.; Petridis, K.; Petrolini, A.; Picatoste Olloqui, E.; Pietrzyk, B.; Pilař, T.; Pinci, D.; Pistone, A.; Playfer, S.; Plo Casasus, M.; Polci, F.; Poluektov, A.; Polycarpo, E.; Popov, A.; Popov, D.; Popovici, B.; Potterat, C.; Price, E.; Prisciandaro, J.; Pritchard, A.; Prouve, C.; Pugatch, V.; Puig Navarro, A.; Punzi, G.; Qian, W.; Rachwal, B.; Rademacker, J. H.; Rakotomiaramanana, B.; Rama, M.; Rangel, M. S.; Raniuk, I.; Rauschmayr, N.; Raven, G.; Reichert, S.; Reid, M. M.; dos Reis, A. C.; Ricciardi, S.; Richards, S.; Rihl, M.; Rinnert, K.; Rives Molina, V.; Roa Romero, D. A.; Robbe, P.; Rodrigues, A. B.; Rodrigues, E.; Rodriguez Perez, P.; Roiser, S.; Romanovsky, V.; Romero Vidal, A.; Rotondo, M.; Rouvinet, J.; Ruf, T.; Ruiz, H.; Ruiz Valls, P.; Saborido Silva, J. J.; Sagidova, N.; Sail, P.; Saitta, B.; Salustino Guimaraes, V.; Sanchez Mayordomo, C.; Sanmartin Sedes, B.; Santacesaria, R.; Santamarina Rios, C.; Santovetti, E.; Sarti, A.; Satriano, C.; Satta, A.; Saunders, D. M.; Savrie, M.; Savrina, D.; Schiller, M.; Schindler, H.; Schlupp, M.; Schmelling, M.; Schmidt, B.; Schneider, O.; Schopper, A.; Schune, M.-H.; Schwemmer, R.; Sciascia, B.; Sciubba, A.; Seco, M.; Semennikov, A.; Sepp, I.; Serra, N.; Serrano, J.; Sestini, L.; Seyfert, P.; Shapkin, M.; Shapoval, I.; Shcheglov, Y.; Shears, T.; Shekhtman, L.; Shevchenko, V.; Shires, A.; Silva Coutinho, R.; Simi, G.; Sirendi, M.; Skidmore, N.; Skwarnicki, T.; Smith, N. A.; Smith, E.; Smith, E.; Smith, J.; Smith, M.; Snoek, H.; Sokoloff, M. D.; Soler, F. J. P.; Soomro, F.; Souza, D.; Souza De Paula, B.; Spaan, B.; Sparkes, A.; Spradlin, P.; Sridharan, S.; Stagni, F.; Stahl, M.; Stahl, S.; Steinkamp, O.; Stenyakin, O.; Stevenson, S.; Stoica, S.; Stone, S.; Storaci, B.; Stracka, S.; Straticiuc, M.; Straumann, U.; Stroili, R.; Subbiah, V. K.; Sun, L.; Sutcliffe, W.; Swientek, K.; Swientek, S.; Syropoulos, V.; Szczekowski, M.; Szczypka, P.; Szilard, D.; Szumlak, T.; T'Jampens, S.; Teklishyn, M.; Tellarini, G.; Teubert, F.; Thomas, C.; Thomas, E.; van Tilburg, J.; Tisserand, V.; Tobin, M.; Tolk, S.; Tomassetti, L.; Tonelli, D.; Topp-Joergensen, S.; Torr, N.; Tournefier, E.; Tourneur, S.; Tran, M. T.; Tresch, M.; Tsaregorodtsev, A.; Tsopelas, P.; Tuning, N.; Ubeda Garcia, M.; Ukleja, A.; Ustyuzhanin, A.; Uwer, U.; Vagnoni, V.; Valenti, G.; Vallier, A.; Vazquez Gomez, R.; Vazquez Regueiro, P.; Vázquez Sierra, C.; Vecchi, S.; Velthuis, J. J.; Veltri, M.; Veneziano, G.; Vesterinen, M.; Viaud, B.; Vieira, D.; Vieites Diaz, M.; Vilasis-Cardona, X.; Vollhardt, A.; Volyanskyy, D.; Voong, D.; Vorobyev, A.; Vorobyev, V.; Voß, C.; Voss, H.; de Vries, J. A.; Waldi, R.; Wallace, C.; Wallace, R.; Walsh, J.; Wandernoth, S.; Wang, J.; Ward, D. R.; Watson, N. K.; Websdale, D.; Whitehead, M.; Wicht, J.; Wiedner, D.; Wilkinson, G.; Williams, M. P.; Williams, M.; Wilson, F. F.; Wimberley, J.; Wishahi, J.; Wislicki, W.; Witek, M.; Wormser, G.; Wotton, S. A.; Wright, S.; Wu, S.; Wyllie, K.; Xie, Y.; Xing, Z.; Xu, Z.; Yang, Z.; Yuan, X.; Yushchenko, O.; Zangoli, M.; Zavertyaev, M.; Zhang, L.; Zhang, W. C.; Zhang, Y.; Zhelezov, A.; Zhokhov, A.; Zhong, L.; Zvyagin, A.; LHCb Collaboration

2014-10-01

A baryonic decay of the Bc+ meson, Bc+→J/ψpp ¯π+, is observed for the first time, with a significance of 7.3 standard deviations, in pp collision data collected with the LHCb detector and corresponding to an integrated luminosity of 3.0 fb-1 taken at center-of-mass energies of 7 and 8 TeV. With the Bc+→J/ψπ+ decay as the normalization channel, the ratio of branching fractions is measured to be B(Bc+→J/ψpp ¯π+)/B(Bc+→J/ψπ+)=0.143-0.034+0.039(stat)±0.013(syst). The mass of the Bc+ meson is determined as M(Bc+)=6274.0±1.8(stat)±0.4(syst) MeV/c2, using the Bc+→J/ψpp ¯π+ channel.

Ventilatory responses to dynamic exercise elicited by intramuscular sensors

NASA Technical Reports Server (NTRS)

Smith, S. A.; Gallagher, K. M.; Norton, K. H.; Querry, R. G.; Welch-O'Connor, R. M.; Raven, P. B.

1999-01-01

PURPOSE: Eight subjects, aged 27.0+/-1.6 yr, performed incremental workload cycling to investigate the contribution of skeletal muscle mechano- and metaboreceptors to ventilatory control during dynamic exercise. METHODS: Each subject performed four bouts of exercise: exercise with no intervention (CON); exercise with bilateral thigh cuffs inflated to 90 mm Hg (CUFF); exercise with application of lower-body positive pressure (LBPP) to 45 torr (PP); and exercise with 90 mm Hg thigh cuff inflation and 45 torr LBPP (CUFF+PP). Ventilatory responses and pulmonary gas exchange variables were collected breath-by-breath with concomitant measurement of leg intramuscular pressure. RESULTS: Ventilation (VE) was significantly elevated from CON during PP and CUFF+PP at workloads corresponding to > or = 60% CON peak oxygen uptake (VO2peak) and during CUFF at workloads > or = 80% CON VO2peak, P < 0.05. The VO2 at which ventilatory threshold occurred was significantly reduced from CON (2.17+/-0.28 L x min(-1)) to 1.60+/-0.19 L x min(-1), 1.45+/-0.15 L x min(-1), and 1.15+/-0.11 L x min(-1) during CUFF, PP, and CUFF+PP, respectively. The slope of the linear regression describing the VE/CO2 output relationship was increased from CON by approximately 22% during CUFF, 40% during PP, and 41% during CUFF+PP. CONCLUSIONS: As intramuscular pressure was significantly elevated immediately upon application of LBPP during PP and CUFF+PP without a concomitant increase in VE, it seems unlikely that LBPP-induced increases in VE can be attributed to activation of the mechanoreflex. These findings suggest that LBPP-induced reductions in perfusion pressure and decreases in venous outflow resulting from inflation of bilateral thigh cuffs may generate a metabolite sensitive intramuscular ventilatory stimulus.

Relationship between compatibilizer and yield strength of PLA/PP Blend

NASA Astrophysics Data System (ADS)

Jariyakulsith, Pattanun; Puajindanetr, Somchai

2018-01-01

The aim of this research is to study the relationship between compatibilizer and yield strength of polylactic acid (PLA) and polypropylene (PP) blend. The PLA is blended with PP (PLA/PP) at the ratios of 70/30, 50/50 and 30/70. In addition, (1) polypropylene grafted maleic anhydride (PP-g-MAH) as a compatibilizer at 0.3 and 0.7 part per hundred of PLA/PP resin (phr) and (2) dicumyl peroxide (DCP) being an initiator at 0.03 and 0.07 phr are added in each composition. Yield strength is characterized to study the interaction between compatibilizer, initiator and yield strength by using experimental design of multilevel full factorial. The results show that (1) the yield strength of PLA/PP blend are increased after addition of compatibilizer. Because the adding of PP-g-MAH and DCP resulted in improving compatibility between PLA and PP. (2) there are interaction between PP-g-MAH and DCP that have affected the final properties of PLA/PP blend. The highest yield strength of 27.68 MPa is provided at the ratio of 70/30 blend by using the 0.3 phr of PP-g-MAH and 0.03 phr of DCP. Linear regression model is fitted and follow the assumptions of normal distribution.

The Ebola Virus Nucleoprotein Recruits the Host PP2A-B56 Phosphatase to Activate Transcriptional Support Activity of VP30.

PubMed

Kruse, Thomas; Biedenkopf, Nadine; Hertz, Emil Peter Thrane; Dietzel, Erik; Stalmann, Gertrud; López-Méndez, Blanca; Davey, Norman E; Nilsson, Jakob; Becker, Stephan

2018-01-04

Transcription of the Ebola virus genome depends on the viral transcription factor VP30 in its unphosphorylated form, but the underlying molecular mechanism of VP30 dephosphorylation is unknown. Here we show that the Ebola virus nucleoprotein (NP) recruits the host PP2A-B56 protein phosphatase through a B56-binding LxxIxE motif and that this motif is essential for VP30 dephosphorylation and viral transcription. The LxxIxE motif and the binding site of VP30 in NP are in close proximity, and both binding sites are required for the dephosphorylation of VP30. We generate a specific inhibitor of PP2A-B56 and show that it suppresses Ebola virus transcription and infection. This work dissects the molecular mechanism of VP30 dephosphorylation by PP2A-B56, and it pinpoints this phosphatase as a potential target for therapeutic intervention. Copyright © 2017 Elsevier Inc. All rights reserved.

Selective Proteasomal Degradation of the B′β Subunit of Protein Phosphatase 2A by the E3 Ubiquitin Ligase Adaptor Kelch-like 15*

PubMed Central

Oberg, Elizabeth A.; Nifoussi, Shanna K.; Gingras, Anne-Claude; Strack, Stefan

2012-01-01

Protein phosphatase 2A (PP2A), a ubiquitous and pleiotropic regulator of intracellular signaling, is composed of a core dimer (AC) bound to a variable (B) regulatory subunit. PP2A is an enzyme family of dozens of heterotrimers with different subcellular locations and cellular substrates dictated by the B subunit. B′β is a brain-specific PP2A regulatory subunit that mediates dephosphorylation of Ca2+/calmodulin-dependent protein kinase II and tyrosine hydroxylase. Unbiased proteomic screens for B′β interactors identified Cullin3 (Cul3), a scaffolding component of E3 ubiquitin ligase complexes, and the previously uncharacterized Kelch-like 15 (KLHL15). KLHL15 is one of ∼40 Kelch-like proteins, many of which have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases. Here, we report that KLHL15-Cul3 specifically targets B′β to promote turnover of the PP2A subunit by ubiquitylation and proteasomal degradation. Comparison of KLHL15 and B′β tissue expression profiles suggests that the E3 ligase adaptor contributes to selective expression of the PP2A/B′β holoenzyme in the brain. We mapped KLHL15 residues critical for homodimerization as well as interaction with Cul3 and B′β. Explaining PP2A subunit selectivity, the divergent N terminus of B′β was found necessary and sufficient for KLHL15-mediated degradation, with Tyr-52 having an obligatory role. Although KLHL15 can interact with the PP2A/B′β heterotrimer, it only degrades B′β, thus promoting exchange with other regulatory subunits. E3 ligase adaptor-mediated control of PP2A holoenzyme composition thereby adds another layer of regulation to cellular dephosphorylation events. PMID:23135275

Analysis of the interactome of the Ser/Thr Protein Phosphatase type 1 in Plasmodium falciparum.

PubMed

Hollin, Thomas; De Witte, Caroline; Lenne, Astrid; Pierrot, Christine; Khalife, Jamal

2016-03-17

Protein Phosphatase 1 (PP1) is an enzyme essential to cell viability in the malaria parasite Plasmodium falciparum (Pf). The activity of PP1 is regulated by the binding of regulatory subunits, of which there are up to 200 in humans, but only 3 have been so far reported for the parasite. To better understand the P. falciparum PP1 (PfPP1) regulatory network, we here report the use of three strategies to characterize the PfPP1 interactome: co-affinity purified proteins identified by mass spectrometry, yeast two-hybrid (Y2H) screening and in silico analysis of the P. falciparum predicted proteome. Co-affinity purification followed by MS analysis identified 6 PfPP1 interacting proteins (Pips) of which 3 contained the RVxF consensus binding, 2 with a Fxx[RK]x[RK] motif, also shown to be a PP1 binding motif and one with both binding motifs. The Y2H screens identified 134 proteins of which 30 present the RVxF binding motif and 20 have the Fxx[RK]x[RK] binding motif. The in silico screen of the Pf predicted proteome using a consensus RVxF motif as template revealed the presence of 55 potential Pips. As further demonstration, 35 candidate proteins were validated as PfPP1 interacting proteins in an ELISA-based assay. To the best of our knowledge, this is the first study on PfPP1 interactome. The data reports several conserved PP1 interacting proteins as well as a high number of specific interactors to PfPP1. Their analysis indicates a high diversity of biological functions for PP1 in Plasmodium. Based on the present data and on an earlier study of the Pf interactome, a potential implication of Pips in protein folding/proteolysis, transcription and pathogenicity networks is proposed. The present work provides a starting point for further studies on the structural basis of these interactions and their functions in P. falciparum.

Uranium hydrogeochemical and stream sediment reconnaissance of the Albuquerque NTMS Quadrangle, New Mexico, including concentrations of forty-three additional elements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maassen, L.W.; Bolivar, S.L.

1979-06-01

The Los Alamos Scientific Laboratory conducted a hydrogeochemical and stream sediment reconnaissance for uranium. Totals of 408 water and 1538 sediment samples were collected from 1802 locations over a 20 100-km/sup 2/ area at an average density of one location per 11 km/sup 2/. Water samples were collected from springs, wells, and streams; sediments samples were collected predominantly from streams, but also from springs. All water samples were analyzed for uranium and 12 other elements. Sediment samples were analyzed for uranium and 42 additional elements. The uranium concentrations in water samples range from below the detection limit of 0.02 ppBmore » to 194.06 ppB. The mean uranium concentration for all water types containing < 40 ppB uranium is 1.98 ppB. Six samples contained uranium concentrations > 40.00 ppB. Well waters have the highest mean uranium concentration; spring waters have the lowest. Clusters of water samples that contain anomalous uranium concentrations are delineated in nine areas. Sediments collected from the quadrangle have uranium concentrations that range between 0.63 ppM and 28.52 ppM, with a mean for all sediments of 3.53 ppM. Eight areas containing clusters of sediments with anomalous uranium concentrations are delineated. One cluster contains sample locations within the Ambrosia Lake uranium district. Five clusters of sediment samples with anomalous uranium concentrations were collected from streams that drain the Jemez volcanic field. Another cluster defines an area just northeast of Albuquerque where streams drain Precambrian rocks, predominantly granites, of the Sandia Mountains. The last cluster, consisting of spring sediments from Mesa Portales, was collected near the contact of the Tertiary Ojo Alamo sandstone with underlying Cretaceous sediments. Sediments from these springs exhibit some of the highest uranium values reported and are associated with high uranium/thorium ratios.« less

Identification of Plasmodium falciparum Translation Initiation eIF2β Subunit: Direct Interaction with Protein Phosphatase Type 1.

PubMed

Tellier, Géraldine; Lenne, Astrid; Cailliau-Maggio, Katia; Cabezas-Cruz, Alejandro; Valdés, James J; Martoriati, Alain; Aliouat, El M; Gosset, Pierre; Delaire, Baptiste; Fréville, Aline; Pierrot, Christine; Khalife, Jamal

2016-01-01

Protein phosphatase 1 (PP1c) is one of the main phosphatases whose function is shaped by many regulators to confer a specific location and a selective function for this enzyme. Here, we report that eukaryotic initiation factor 2β of Plasmodium falciparum (PfeIF2β) is an interactor of PfPP1c. Sequence analysis of PfeIF2β revealed a deletion of 111 amino acids when compared to its human counterpart and the presence of two potential binding motifs to PfPP1 ((29)FGEKKK(34), (103)KVAW(106)). As expected, we showed that PfeIF2β binds PfeIF2γ and PfeIF5, confirming its canonical interaction with partners of the translation complex. Studies of the PfeIF2β-PfPP1 interaction using wild-type, single and double mutated versions of PfeIF2β revealed that both binding motifs are critical. We next showed that PfeIF2β is able to induce Germinal Vesicle Break Down (GVBD) when expressed in Xenopus oocytes, an indicator of its capacity to regulate PP1. Only combined mutations of both binding motifs abolished the interaction with PP1 and the induction of GVBD. In P. falciparum, although the locus is accessible for genetic manipulation, PfeIF2β seems to play an essential role in intraerythrocytic cycle as no viable knockout parasites were detectable. Interestingly, as for PfPP1, the subcellular fractionation of P. falciparum localized PfeIF2β in cytoplasm and nuclear extracts, suggesting a potential effect on PfPP1 in both compartments and raising the question of a non-canonical function of PfeIf2β in the nucleus. Hence, the role played by PfeIF2β in blood stage parasites could occur at multiple levels involving the binding to proteins of the translational complex and to PfPP1.

Measurement of the B ± production cross-section in pp collisions at √{s}=7 and 13 TeV

NASA Astrophysics Data System (ADS)

Aaij, R.; Adeva, B.; Adinolfi, M.; Ajaltouni, Z.; Akar, S.; Albrecht, J.; Alessio, F.; Alexander, M.; Alfonso Albero, A.; Ali, S.; Alkhazov, G.; Alvarez Cartelle, P.; Alves, A. A.; Amato, S.; Amerio, S.; Amhis, Y.; An, L.; Anderlini, L.; Andreassi, G.; Andreotti, M.; Andrews, J. E.; Appleby, R. B.; Archilli, F.; d'Argent, P.; Arnau Romeu, J.; Artamonov, A.; Artuso, M.; Aslanides, E.; Atzeni, M.; Auriemma, G.; Baalouch, M.; Babuschkin, I.; Bachmann, S.; Back, J. J.; Badalov, A.; Baesso, C.; Baker, S.; Balagura, V.; Baldini, W.; Baranov, A.; Barlow, R. J.; Barschel, C.; Barsuk, S.; Barter, W.; Baryshnikov, F.; Batozskaya, V.; Battista, V.; Bay, A.; Beaucourt, L.; Beddow, J.; Bedeschi, F.; Bediaga, I.; Beiter, A.; Bel, L. J.; Beliy, N.; Bellee, V.; Belloli, N.; Belous, K.; Belyaev, I.; Ben-Haim, E.; Bencivenni, G.; Benson, S.; Beranek, S.; Berezhnoy, A.; Bernet, R.; Berninghoff, D.; Bertholet, E.; Bertolin, A.; Betancourt, C.; Betti, F.; Bettler, M.-O.; van Beuzekom, M.; Bezshyiko, Ia.; Bifani, S.; Billoir, P.; Birnkraut, A.; Bizzeti, A.; Bjørn, M.; Blake, T.; Blanc, F.; Blusk, S.; Bocci, V.; Boettcher, T.; Bondar, A.; Bondar, N.; Bordyuzhin, I.; Borghi, S.; Borisyak, M.; Borsato, M.; Bossu, F.; Boubdir, M.; Bowcock, T. J. V.; Bowen, E.; Bozzi, C.; Braun, S.; Britton, T.; Brodzicka, J.; Brundu, D.; Buchanan, E.; Burr, C.; Bursche, A.; Buytaert, J.; Byczynski, W.; Cadeddu, S.; Cai, H.; Calabrese, R.; Calladine, R.; Calvi, M.; Calvo Gomez, M.; Camboni, A.; Campana, P.; Campora Perez, D. H.; Capriotti, L.; Carbone, A.; Carboni, G.; Cardinale, R.; Cardini, A.; Carniti, P.; Carson, L.; Carvalho Akiba, K.; Casse, G.; Cassina, L.; Cattaneo, M.; Cavallero, G.; Cenci, R.; Chamont, D.; Chapman, M. G.; Charles, M.; Charpentier, Ph.; Chatzikonstantinidis, G.; Chefdeville, M.; Chen, S.; Cheung, S. F.; Chitic, S.-G.; Chobanova, V.; Chrzaszcz, M.; Chubykin, A.; Ciambrone, P.; Cid Vidal, X.; Ciezarek, G.; Clarke, P. E. L.; Clemencic, M.; Cliff, H. V.; Closier, J.; Cogan, J.; Cogneras, E.; Cogoni, V.; Cojocariu, L.; Collins, P.; Colombo, T.; Comerma-Montells, A.; Contu, A.; Cook, A.; Coombs, G.; Coquereau, S.; Corti, G.; Corvo, M.; Costa Sobral, C. M.; Couturier, B.; Cowan, G. A.; Craik, D. C.; Crocombe, A.; Cruz Torres, M.; Currie, R.; D'Ambrosio, C.; Da Cunha Marinho, F.; Dall'Occo, E.; Dalseno, J.; Davis, A.; De Aguiar Francisco, O.; De Capua, S.; De Cian, M.; De Miranda, J. M.; De Paula, L.; De Serio, M.; De Simone, P.; Dean, C. T.; Decamp, D.; Del Buono, L.; Dembinski, H.-P.; Demmer, M.; Dendek, A.; Derkach, D.; Deschamps, O.; Dettori, F.; Dey, B.; Di Canto, A.; Di Nezza, P.; Dijkstra, H.; Dordei, F.; Dorigo, M.; Dosil Suárez, A.; Douglas, L.; Dovbnya, A.; Dreimanis, K.; Dufour, L.; Dujany, G.; Durante, P.; Dzhelyadin, R.; Dziewiecki, M.; Dziurda, A.; Dzyuba, A.; Easo, S.; Ebert, M.; Egede, U.; Egorychev, V.; Eidelman, S.; Eisenhardt, S.; Eitschberger, U.; Ekelhof, R.; Eklund, L.; Ely, S.; Esen, S.; Evans, H. M.; Evans, T.; Falabella, A.; Farley, N.; Farry, S.; Fazzini, D.; Federici, L.; Ferguson, D.; Fernandez, G.; Fernandez Declara, P.; Fernandez Prieto, A.; Ferrari, F.; Ferreira Rodrigues, F.; Ferro-Luzzi, M.; Filippov, S.; Fini, R. A.; Fiorini, M.; Firlej, M.; Fitzpatrick, C.; Fiutowski, T.; Fleuret, F.; Fohl, K.; Fontana, M.; Fontanelli, F.; Forshaw, D. C.; Forty, R.; Franco Lima, V.; Frank, M.; Frei, C.; Fu, J.; Funk, W.; Furfaro, E.; Färber, C.; Gabriel, E.; Gallas Torreira, A.; Galli, D.; Gallorini, S.; Gambetta, S.; Gandelman, M.; Gandini, P.; Gao, Y.; Garcia Martin, L. M.; García Pardiñas, J.; Garra Tico, J.; Garrido, L.; Garsed, P. J.; Gascon, D.; Gaspar, C.; Gavardi, L.; Gazzoni, G.; Gerick, D.; Gersabeck, E.; Gersabeck, M.; Gershon, T.; Ghez, Ph.; Gianì, S.; Gibson, V.; Girard, O. G.; Giubega, L.; Gizdov, K.; Gligorov, V. V.; Golubkov, D.; Golutvin, A.; Gomes, A.; Gorelov, I. V.; Gotti, C.; Govorkova, E.; Grabowski, J. P.; Graciani Diaz, R.; Granado Cardoso, L. A.; Graugés, E.; Graverini, E.; Graziani, G.; Grecu, A.; Greim, R.; Griffith, P.; Grillo, L.; Gruber, L.; Gruberg Cazon, B. R.; Grünberg, O.; Gushchin, E.; Guz, Yu.; Gys, T.; Göbel, C.; Hadavizadeh, T.; Hadjivasiliou, C.; Haefeli, G.; Haen, C.; Haines, S. C.; Hamilton, B.; Han, X.; Hancock, T. H.; Hansmann-Menzemer, S.; Harnew, N.; Harnew, S. T.; Hasse, C.; Hatch, M.; He, J.; Hecker, M.; Heinicke, K.; Heister, A.; Hennessy, K.; Henrard, P.; Henry, L.; van Herwijnen, E.; Heß, M.; Hicheur, A.; Hill, D.; Hombach, C.; Hopchev, P. H.; Hu, W.; Huard, Z. C.; Hulsbergen, W.; Humair, T.; Hushchyn, M.; Hutchcroft, D.; Ibis, P.; Idzik, M.; Ilten, P.; Jacobsson, R.; Jalocha, J.; Jans, E.; Jawahery, A.; Jiang, F.; John, M.; Johnson, D.; Jones, C. R.; Joram, C.; Jost, B.; Jurik, N.; Kandybei, S.; Karacson, M.; Kariuki, J. M.; Karodia, S.; Kazeev, N.; Kecke, M.; Keizer, F.; Kelsey, M.; Kenzie, M.; Ketel, T.; Khairullin, E.; Khanji, B.; Khurewathanakul, C.; Kirn, T.; Klaver, S.; Klimaszewski, K.; Klimkovich, T.; Koliiev, S.; Kolpin, M.; Kopecna, R.; Koppenburg, P.; Kosmyntseva, A.; Kotriakhova, S.; Kozeiha, M.; Kravchuk, L.; Kreps, M.; Kress, F.; Krokovny, P.; Kruse, F.; Krzemien, W.; Kucewicz, W.; Kucharczyk, M.; Kudryavtsev, V.; Kuonen, A. K.; Kvaratskheliya, T.; Lacarrere, D.; Lafferty, G.; Lai, A.; Lanfranchi, G.; Langenbruch, C.; Latham, T.; Lazzeroni, C.; Le Gac, R.; Leflat, A.; Lefrançois, J.; Lefèvre, R.; Lemaitre, F.; Lemos Cid, E.; Leroy, O.; Lesiak, T.; Leverington, B.; Li, P.-R.; Li, T.; Li, Y.; Li, Z.; Likhomanenko, T.; Lindner, R.; Lionetto, F.; Lisovskyi, V.; Liu, X.; Loh, D.; Loi, A.; Longstaff, I.; Lopes, J. H.; Lucchesi, D.; Lucio Martinez, M.; Luo, H.; Lupato, A.; Luppi, E.; Lupton, O.; Lusiani, A.; Lyu, X.; Machefert, F.; Maciuc, F.; Macko, V.; Mackowiak, P.; Maddrell-Mander, S.; Maev, O.; Maguire, K.; Maisuzenko, D.; Majewski, M. W.; Malde, S.; Malecki, B.; Malinin, A.; Maltsev, T.; Manca, G.; Mancinelli, G.; Marangotto, D.; Maratas, J.; Marchand, J. F.; Marconi, U.; Marin Benito, C.; Marinangeli, M.; Marino, P.; Marks, J.; Martellotti, G.; Martin, M.; Martinelli, M.; Martinez Santos, D.; Martinez Vidal, F.; Massacrier, L. M.; Massafferri, A.; Matev, R.; Mathad, A.; Mathe, Z.; Matteuzzi, C.; Mauri, A.; Maurice, E.; Maurin, B.; Mazurov, A.; McCann, M.; McNab, A.; McNulty, R.; Mead, J. V.; Meadows, B.; Meaux, C.; Meier, F.; Meinert, N.; Melnychuk, D.; Merk, M.; Merli, A.; Michielin, E.; Milanes, D. A.; Millard, E.; Minard, M.-N.; Minzoni, L.; Mitzel, D. S.; Mogini, A.; Molina Rodriguez, J.; Mombächer, T.; Monroy, I. A.; Monteil, S.; Morandin, M.; Morello, M. J.; Morgunova, O.; Moron, J.; Morris, A. B.; Mountain, R.; Muheim, F.; Mulder, M.; Müller, D.; Müller, J.; Müller, K.; Müller, V.; Naik, P.; Nakada, T.; Nandakumar, R.; Nandi, A.; Nasteva, I.; Needham, M.; Neri, N.; Neubert, S.; Neufeld, N.; Neuner, M.; Nguyen, T. D.; Nguyen-Mau, C.; Nieswand, S.; Niet, R.; Nikitin, N.; Nikodem, T.; Nogay, A.; O'Hanlon, D. P.; Oblakowska-Mucha, A.; Obraztsov, V.; Ogilvy, S.; Oldeman, R.; Onderwater, C. J. G.; Ossowska, A.; Otalora Goicochea, J. M.; Owen, P.; Oyanguren, A.; Pais, P. R.; Palano, A.; Palutan, M.; Papanestis, A.; Pappagallo, M.; Pappalardo, L. L.; Parker, W.; Parkes, C.; Passaleva, G.; Pastore, A.; Patel, M.; Patrignani, C.; Pearce, A.; Pellegrino, A.; Penso, G.; Pepe Altarelli, M.; Perazzini, S.; Perret, P.; Pescatore, L.; Petridis, K.; Petrolini, A.; Petrov, A.; Petruzzo, M.; Picatoste Olloqui, E.; Pietrzyk, B.; Pikies, M.; Pinci, D.; Pisani, F.; Pistone, A.; Piucci, A.; Placinta, V.; Playfer, S.; Plo Casasus, M.; Polci, F.; Poli Lener, M.; Poluektov, A.; Polyakov, I.; Polycarpo, E.; Pomery, G. J.; Ponce, S.; Popov, A.; Popov, D.; Poslavskii, S.; Potterat, C.; Price, E.; Prisciandaro, J.; Prouve, C.; Pugatch, V.; Puig Navarro, A.; Pullen, H.; Punzi, G.; Qian, W.; Quagliani, R.; Quintana, B.; Rachwal, B.; Rademacker, J. H.; Rama, M.; Ramos Pernas, M.; Rangel, M. S.; Raniuk, I.; Ratnikov, F.; Raven, G.; Ravonel Salzgeber, M.; Reboud, M.; Redi, F.; Reichert, S.; dos Reis, A. C.; Remon Alepuz, C.; Renaudin, V.; Ricciardi, S.; Richards, S.; Rihl, M.; Rinnert, K.; Rives Molina, V.; Robbe, P.; Robert, A.; Rodrigues, A. B.; Rodrigues, E.; Rodriguez Lopez, J. A.; Rogozhnikov, A.; Roiser, S.; Rollings, A.; Romanovskiy, V.; Romero Vidal, A.; Ronayne, J. W.; Rotondo, M.; Rudolph, M. S.; Ruf, T.; Ruiz Valls, P.; Ruiz Vidal, J.; Saborido Silva, J. J.; Sadykhov, E.; Sagidova, N.; Saitta, B.; Salustino Guimaraes, V.; Sanchez Mayordomo, C.; Sanmartin Sedes, B.; Santacesaria, R.; Santamarina Rios, C.; Santimaria, M.; Santovetti, E.; Sarpis, G.; Sarti, A.; Satriano, C.; Satta, A.; Saunders, D. M.; Savrina, D.; Schael, S.; Schellenberg, M.; Schiller, M.; Schindler, H.; Schmelling, M.; Schmelzer, T.; Schmidt, B.; Schneider, O.; Schopper, A.; Schreiner, H. F.; Schubiger, M.; Schune, M.-H.; Schwemmer, R.; Sciascia, B.; Sciubba, A.; Semennikov, A.; Sepulveda, E. S.; Sergi, A.; Serra, N.; Serrano, J.; Sestini, L.; Seyfert, P.; Shapkin, M.; Shapoval, I.; Shcheglov, Y.; Shears, T.; Shekhtman, L.; Shevchenko, V.; Siddi, B. G.; Silva Coutinho, R.; Silva de Oliveira, L.; Simi, G.; Simone, S.; Sirendi, M.; Skidmore, N.; Skwarnicki, T.; Smith, E.; Smith, I. T.; Smith, J.; Smith, M.; Soares Lavra, l.; Sokoloff, M. D.; Soler, F. J. P.; Souza De Paula, B.; Spaan, B.; Spradlin, P.; Sridharan, S.; Stagni, F.; Stahl, M.; Stahl, S.; Stefko, P.; Stefkova, S.; Steinkamp, O.; Stemmle, S.; Stenyakin, O.; Stepanova, M.; Stevens, H.; Stone, S.; Storaci, B.; Stracka, S.; Stramaglia, M. E.; Straticiuc, M.; Straumann, U.; Sun, J.; Sun, L.; Sutcliffe, W.; Swientek, K.; Syropoulos, V.; Szumlak, T.; Szymanski, M.; T'Jampens, S.; Tayduganov, A.; Tekampe, T.; Tellarini, G.; Teubert, F.; Thomas, E.; van Tilburg, J.; Tilley, M. J.; Tisserand, V.; Tobin, M.; Tolk, S.; Tomassetti, L.; Tonelli, D.; Toriello, F.; Tourinho Jadallah Aoude, R.; Tournefier, E.; Traill, M.; Tran, M. T.; Tresch, M.; Trisovic, A.; Tsaregorodtsev, A.; Tsopelas, P.; Tully, A.; Tuning, N.; Ukleja, A.; Usachov, A.; Ustyuzhanin, A.; Uwer, U.; Vacca, C.; Vagner, A.; Vagnoni, V.; Valassi, A.; Valat, S.; Valenti, G.; Vazquez Gomez, R.; Vazquez Regueiro, P.; Vecchi, S.; van Veghel, M.; Velthuis, J. J.; Veltri, M.; Veneziano, G.; Venkateswaran, A.; Verlage, T. A.; Vernet, M.; Vesterinen, M.; Viana Barbosa, J. V.; Viaud, B.; Vieira, D.; Vieites Diaz, M.; Viemann, H.; Vilasis-Cardona, X.; Vitti, M.; Volkov, V.; Vollhardt, A.; Voneki, B.; Vorobyev, A.; Vorobyev, V.; Voß, C.; de Vries, J. A.; Vázquez Sierra, C.; Waldi, R.; Wallace, C.; Wallace, R.; Walsh, J.; Wang, J.; Ward, D. R.; Wark, H. M.; Watson, N. K.; Websdale, D.; Weiden, A.; Weisser, C.; Whitehead, M.; Wicht, J.; Wilkinson, G.; Wilkinson, M.; Williams, M.; Williams, M. P.; Williams, M.; Williams, T.; Wilson, F. F.; Wimberley, J.; Winn, M.; Wishahi, J.; Wislicki, W.; Witek, M.; Wormser, G.; Wotton, S. A.; Wraight, K.; Wyllie, K.; Xie, Y.; Xu, M.; Xu, Z.; Yang, Z.; Yang, Z.; Yao, Y.; Yin, H.; Yu, J.; Yuan, X.; Yushchenko, O.; Zarebski, K. A.; Zavertyaev, M.; Zhang, L.; Zhang, Y.; Zhelezov, A.; Zheng, Y.; Zhu, X.; Zhukov, V.; Zonneveld, J. B.; Zucchelli, S.

2017-12-01

The production of B ± mesons is studied in pp collisions at centre-of-mass energies of 7 and 13 TeV, using B ± → J/ ψ K ± decays and data samples corresponding to 1.0 fb-1 and 0.3 fb-1, respectively. The production cross-sections summed over both charges and integrated over the transverse momentum range 0 < p T < 40 GeV/ c and the rapidity range 2.0 < y < 4.5 are measured to be σ ( pp\\to {B}^{± }X,√{s}=7 TeV)=43.0± 0.2± 2.5± 1.7 μ b, σ ( pp\\to {B}^{± }X,√{s}=13 TeV)=86.6± 0.5± 5.4± 3.4 μ b, where the first uncertainties are statistical, the second are systematic, and the third are due to the limited knowledge of the B ± → J/ ψ K ± branching fraction. The ratio of the cross-section at 13 TeV to that at 7 TeV is determined to be 2.02 ± 0.02 (stat) ± 0.12 (syst). Differential cross-sections are also reported as functions of p T and y. All results are in agreement with theoretical calculations based on the state-of-art fixed next-to-leading order quantum chromodynamics. [Figure not available: see fulltext.

Tributyltin induces a G2/M cell cycle arrest in human amniotic cells via PP2A inhibition-mediated inactivation of the ERK1/2 cascades.

PubMed

Zhang, Yali; Guo, Zonglou; Xu, Lihong

2014-03-01

The molecular mechanisms underlying the cell cycle alterations induced by tributyltin (TBT), a highly toxic environmental contaminant, remain elusive. In this study, cell cycle progression and some key regulators in G2/M phase were investigated in human amniotic cells treated with TBT. Furthermore, protein phosphatase (PP) 2A and the ERK cascades were examined. The results showed that TBT caused a G2/M cell cycle arrest that was accompanied by a decrease in the total cdc25C protein level and an increase in the p-cdc2 level in the nucleus. TBT caused a decrease in PP2A activity and inhibited the ERK cascade by inactivating Raf-1, resulting in the dephosphorylation of MEK1/2, ERK1/2, and c-Myc. Taken together, TBT leads to a G2/M cell cycle arrest in FL cells, an increase in p-cdc2 and a decrease in the levels of total cdc25C protein, which may be caused by the PP2A inhibition-mediated inactivation of the ERK1/2 cascades. Copyright © 2014 Elsevier B.V. All rights reserved.

Protein Phosphatase 2A Signaling in Human Prostate Cancer

DTIC Science & Technology

2014-08-01

transfectants. Later, these cells were characterized for the PP2Acα expression and activity by immunoblot and malachite green based assay, respectively. Data...After centrifugation, 25 mL of supernatant was transferred to an assay plate; 100 mL of Malachite Green phosphate detection solution was added and incu...cancer cells was resolved and immunoblotted for PP2AC and b-actin (internal control). PP2A activity was determined by malachite green–based

Piperazines for peptide carboxyl group derivatization: effect of derivatization reagents and properties of peptides on signal enhancement in matrix-assisted laser desorption/ionization mass spectrometry.

PubMed

Qiao, Xiaoqiang; Sun, Liangliang; Chen, Lingfan; Zhou, Yuan; Yang, Kaiguang; Liang, Zhen; Zhang, Lihua; Zhang, Yukui

2011-03-15

Piperazine-based derivatives, including 1-(2-pyridyl)piperazine (2-PP), 1-(2-pyrimidyl)piperazine (2-PMP), 1-(4-pyridyl)piperazine (4-PP), and 1-(1-methyl-4-piperidinyl)piperazine (M-PP), were used for the derivatization of carboxyl groups on peptides with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and 1-hydroxy-7-azabenzotriazole (HOAt) as coupling reagents, and trifluoroacetic acid (TFA) as activator. Taking synthetic peptides RVYVHPI (RI-7) and APGDRIYVHPF (AF-11) as samples, the yields of derivatized peptides by 2-PP, 2-PMP and 4-PP were higher than 94%. The effect of piperazine derivatives on the signals of tryptic digests of α-transferrin and bovine serum albumin (BSA) was investigated, and it was found that peptides derivatized by 2-PP and 2-PMP exhibited obviously improved ionization efficiency. Furthermore, comparison of identified peptides before and after derivatization showed that peptides with low molecular weight (MW) and high pI value were preferably detected after derivatization. In addition, after derivatization with 2-PP and 2-PMP, protein myelin basic protein S, 20 kDa protein, and histone H were confidently identified from the tryptic digests of two fractions of rat brain protein separated by reversed-phase high-performance liquid chromatography (HPLC), indicating the potential application of 2-PP and 2-PMP for the highly sensitive determination of peptides in comprehensive proteome analysis. Copyright © 2011 John Wiley & Sons, Ltd.

Physalis peruviana L. inhibits airway inflammation induced by cigarette smoke and lipopolysaccharide through inhibition of extracellular signal-regulated kinase and induction of heme oxygenase-1.

PubMed

Park, Hyun Ah; Lee, Jae-Won; Kwon, Ok-Kyoung; Lee, Gilhye; Lim, Yourim; Kim, Jung Hee; Paik, Jin-Hyub; Choi, Sangho; Paryanto, Imam; Yuniato, Prasetyawan; Kim, Doo-Young; Ryu, Hyung Won; Oh, Sei-Ryang; Lee, Seung Jin; Ahn, Kyung-Seop

2017-11-01

Physalis peruviana L. (PP) is a medicinal herb that has been confirmed to have several biological activities, including anticancer, antioxidant and anti-inflammatory properties. The aim of the present study was to evaluate the protective effect of PP on cigarette smoke (CS)- and lipopolysaccharide (LPS)-induced pulmonary inflammation. Treatment with PP significantly reduced the influx of inflammatory cells in the bronchoalveolar lavage fluid (BALF) and lung of mice with CS- and LPS-induced pulmonary inflammation. PP also decreased the levels of reactive oxygen species (ROS) and pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the BALF. PP effectively attenuated the expression of monocyte chemoattractant protein-1 (MCP-1) and the activation of extracellular signal-regulated kinase (ERK) in the lung. In addition, nuclear factor erythroid 2-related factor 2 (Nrf2) activation and heme oxygenase-1 (HO-1) expression were increased by PP treatment. In an in vitro experiment, PP reduced the mRNA expression of TNF-α and MCP-1, and the activation of ERK in CS extract-stimulated A549 epithelial cells. Furthermore, PP increased the activation of Nrf2 and the expression of HO-1 in A549 cells. These findings suggest that PP has a therapeutic potential for the treatment of pulmonary inflammatory diseases, such as chronic obstructive pulmonary disease.

Study of J/ψ→pp̄ and J/ψ→nn̄

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ablikim, M.; Achasov, M. N.; Ambrose, D. J.

2012-08-31

The decays J/ψ→pp̄ and J/ψ→nn̄ have been investigated with a sample of 225.2×10⁶ J/ψ events collected with the BESIII detector at the BEPCII e⁺e⁻ collider. The branching fractions are determined to be B(J/ψ→pp̄)=(2.112±0.004±0.031)×10⁻³ and B(J/ψ→nn̄)=(2.07±0.01±0.17)×10⁻³. Distributions of the angle θ between the proton or antineutron and the beam direction are well described by the form 1+αcos²θ, and we find α=0.595±0.012±0.015 for J/ψ→pp̄ and α=0.50±0.04±0.21 for J/ψ→nn̄. Our branching-fraction results suggest a large phase angle between the strong and electromagnetic amplitudes describing the J/ψ→NN¯¯¯ decay.

Structure–Activity Relationship Studies Using Natural and Synthetic Okadaic Acid/Dinophysistoxin Toxins

PubMed Central

Twiner, Michael J.; Doucette, Gregory J.; Pang, Yucheng; Fang, Chao; Forsyth, Craig J.; Miles, Christopher O.

2016-01-01

Okadaic acid (OA) and the closely related dinophysistoxins (DTXs) are algal toxins that accumulate in shellfish and are known serine/threonine protein phosphatase (ser/thr PP) inhibitors. Phosphatases are important modulators of enzyme activity and cell signaling pathways. However, the interactions between the OA/DTX toxins and phosphatases are not fully understood. This study sought to identify phosphatase targets and characterize their structure–activity relationships (SAR) with these algal toxins using a combination of phosphatase activity and cytotoxicity assays. Preliminary screening of 21 human and yeast phosphatases indicated that only three ser/thr PPs (PP2a, PP1, PP5) were inhibited by physiologically saturating concentrations of DTX2 (200 nM). SAR studies employed naturally-isolated OA, DTX1, and DTX2, which vary in degree and/or position of methylation, in addition to synthetic 2-epi-DTX2. OA/DTX analogs induced cytotoxicity and inhibited PP activity with a relatively conserved order of potency: OA = DTX1 ≥ DTX2 >> 2-epi-DTX. The PPs were also differentially inhibited with sensitivities of PP2a > PP5 > PP1. These findings demonstrate that small variations in OA/DTX toxin structures, particularly at the head region (i.e., C1/C2), result in significant changes in toxicological potency, whereas changes in methylation at C31 and C35 (tail region) only mildly affect potency. In addition to this being the first study to extensively test OA/DTX analogs’ activities towards PP5, these data will be helpful for accurately determining toxic equivalence factors (TEFs), facilitating molecular modeling efforts, and developing highly selective phosphatase inhibitors. PMID:27827901

PP2A: more than a reset switch to activate pRB proteins during the cell cycle and in response to signaling cues

PubMed Central

Kurimchak, Alison; Graña, Xavier

2015-01-01

In their active hypophosphorylated state, members of the retinoblastoma family of pocket proteins negatively regulate cell cycle progression at least in part by repressing expression of E2F-dependent genes. Mitogen-dependent activation of G1 and G1/S Cyclin Dependent Kinases (CDKs) results in coordinated hyperphosphorylation and inactivation of these proteins, which no longer bind and repress E2Fs. S and G2/M CDKs maintain pocket protein hyperphosphorylated through the end of mitosis. The inactivating action of inducible CDKs is opposed by the Ser/Thr protein phosphatases PP2A and PP1. Various trimeric PP2A holoenzymes have been implicated in dephosphorylation of pocket proteins in response to specific cellular signals and stresses or as part of an equilibrium with CDKs throughout the cell cycle. PP1 has specifically been implicated in dephosphorylation of pRB in late mitosis and early G1. This review is particularly focused on the emerging role of PP2A as a major hub for integration of growth suppressor signals that require rapid inactivation of pocket proteins. Of note, activation of particular PP2A holoenzymes triggers differential activation of pocket proteins in the presence of active CDKs.

The ‘spiteful’ origins of human cooperation

PubMed Central

Marlowe, Frank W.; Berbesque, J. Colette; Barrett, Clark; Bolyanatz, Alexander; Gurven, Michael; Tracer, David

2011-01-01

We analyse generosity, second-party (‘spiteful’) punishment (2PP), and third-party (‘altruistic’) punishment (3PP) in a cross-cultural experimental economics project. We show that smaller societies are less generous in the Dictator Game but no less prone to 2PP in the Ultimatum Game. We might assume people everywhere would be more willing to punish someone who hurt them directly (2PP) than someone who hurt an anonymous third person (3PP). While this is true of small societies, people in large societies are actually more likely to engage in 3PP than 2PP. Strong reciprocity, including generous offers and 3PP, exists mostly in large, complex societies that face numerous challenging collective action problems. We argue that ‘spiteful’ 2PP, motivated by the basic emotion of anger, is more universal than 3PP and sufficient to explain the origins of human cooperation. PMID:21159680

The 'spiteful' origins of human cooperation.

PubMed

Marlowe, Frank W; Berbesque, J Colette; Barrett, Clark; Bolyanatz, Alexander; Gurven, Michael; Tracer, David

2011-07-22

We analyse generosity, second-party ('spiteful') punishment (2PP), and third-party ('altruistic') punishment (3PP) in a cross-cultural experimental economics project. We show that smaller societies are less generous in the Dictator Game but no less prone to 2PP in the Ultimatum Game. We might assume people everywhere would be more willing to punish someone who hurt them directly (2PP) than someone who hurt an anonymous third person (3PP). While this is true of small societies, people in large societies are actually more likely to engage in 3PP than 2PP. Strong reciprocity, including generous offers and 3PP, exists mostly in large, complex societies that face numerous challenging collective action problems. We argue that 'spiteful' 2PP, motivated by the basic emotion of anger, is more universal than 3PP and sufficient to explain the origins of human cooperation.

Prediction of first-trimester preeclampsia: Relevance of the oxidative stress marker MDA in a combination model with PP-13, PAPP-A and beta-HCG.

PubMed

Asiltas, Burak; Surmen-Gur, Esma; Uncu, Gurkan

2018-02-27

Early diagnosis of preeclampsia (PE) is very important and various parameters, individually or in combined models, are reported useful for prediction of PE. The objective of this study is to investigate the predictive value of pregnancy-associated plasma protein-A (PAPP-A), placental protein-13 (PP-13), human Chorionic Gonadotropin (B-HCG), and oxidative stress marker malondialdehyde (MDA), individually and in combination. Maternal sera of 38 cases with PE and 122 controls were collected for first trimester screening and tested for PAPP-A and B-HCG by chemiluminescence, for PP-13 by using ELISA, and for MDA by high-performance liquid chromatography. Combined models of parameters were constituted as "MDA + PP-13", "PP-13 + PAPP-A + B-HCG" and "MDA + PP-13 + PAPP-A + B-HCG". The diagnostic performances of serum markers of preeclampsia were examined by nonparametric receiver-operator characteristics (ROC) analysis. PP-13 levels were significantly lower (p < 0.001) and MDA levels were significantly higher (p < 0.001) in PE. The area under the ROC curve (AUC) for MDA and PP-13 were greater than those for PAPP-A and B-HCG (p < 0.001). The AUCs of the combined models were significantly larger than those of individual parameters. The combined model "MDA + PP-13 + PAPP-A + B-HCG" exhibited the best predictive outcome with an AUC of 0.91 [95% CI 0.86-0.95], 97% [95% CI 86.2-99.9] sensitivity and 75% [95% CI 66.5-82.6] specificity, and was significantly different from that of "PAPP-A + PP-13 + B-HCG" model, but similar to that of "MDA + PP-13" model. Combined models consisting of various parameters of different origin, may provide better predictive outcomes, and oxidative markers should be considered in combination with other placental biomarkers in prediction of PE. Copyright © 2018 Elsevier B.V. All rights reserved.

The Human Adenovirus Type 5 E4orf4 Protein Targets Two Phosphatase Regulators of the Hippo Signaling Pathway

PubMed Central

Mui, Melissa Z.; Zhou, Yiwang; Blanchette, Paola; Chughtai, Naila; Knight, Jennifer F.; Gruosso, Tina; Papadakis, Andreas I.; Huang, Sidong; Park, Morag; Gingras, Anne-Claude

2015-01-01

ABSTRACT When expressed alone at high levels, the human adenovirus E4orf4 protein exhibits tumor cell-specific p53-independent toxicity. A major E4orf4 target is the B55 class of PP2A regulatory subunits, and we have shown recently that binding of E4orf4 inhibits PP2AB55 phosphatase activity in a dose-dependent fashion by preventing access of substrates (M. Z. Mui et al., PLoS Pathog 9:e1003742, 2013, http://dx.doi.org/10.1371/journal.ppat.1003742). While interaction with B55 subunits is essential for toxicity, E4orf4 mutants exist that, despite binding B55 at high levels, are defective in cell killing, suggesting that other essential targets exist. In an attempt to identify additional targets, we undertook a proteomics approach to characterize E4orf4-interacting proteins. Our findings indicated that, in addition to PP2AB55 subunits, ASPP-PP1 complex subunits were found among the major E4orf4-binding species. Both the PP2A and ASPP-PP1 phosphatases are known to positively regulate effectors of the Hippo signaling pathway, which controls the expression of cell growth/survival genes by dephosphorylating the YAP transcriptional coactivator. We find here that expression of E4orf4 results in hyperphosphorylation of YAP, suggesting that Hippo signaling is affected by E4orf4 interactions with PP2AB55 and/or ASPP-PP1 phosphatases. Furthermore, knockdown of YAP1 expression was seen to enhance E4orf4 killing, again consistent with a link between E4orf4 toxicity and inhibition of the Hippo pathway. This effect may in fact contribute to the cancer cell specificity of E4orf4 toxicity, as many human cancer cells rely heavily on the Hippo pathway for their enhanced proliferation. IMPORTANCE The human adenovirus E4orf4 protein has been known for some time to induce tumor cell-specific death when expressed at high levels; thus, knowledge of its mode of action could be of importance for development of new cancer therapies. Although the B55 form of the phosphatase PP2A has long been known as an essential E4orf4 target, genetic analyses indicated that others must exist. To identify additional E4orf4 targets, we performed, for the first time, a large-scale affinity purification/mass spectrometry analysis of E4orf4 binding partners. Several additional candidates were detected, including key regulators of the Hippo signaling pathway, which enhances cell viability in many cancers, and results of preliminary studies suggested a link between inhibition of Hippo signaling and E4orf4 toxicity. PMID:26085163

The spectroscopy analyses of PpIX by ultrasound irradiation and its sonotoxicity in vitro.

PubMed

Wang, Pan; Wang, Xiaobing; Zhang, Kun; Gao, Kaili; Song, Ming; Liu, Quanhong

2013-07-01

Protoporphyrin IX (PpIX) has been used as a sensitizer in photodynamic therapy (PDT) as well as in sonodynamic therapy (SDT). The photo-bleaching of PpIX has been well investigated in many experimental systems and some photo-products have also been identified in PDT. But until now, little information has been reported about the sono-damage of PpIX in SDT. So, the present study was to investigate changes of PpIX properties before and after different ultrasound treatment, and the potential interactions between PpIX, ultrasound and the irradiated cells. In cell-free system, the absorption and fluorescence spectra of PpIX in different solutions were measured by ultraviolet spectrometer and fluorescence spectrophotometer, respectively. The terephthalic acid dosimetry was applied to evaluate the efficiency of ultrasound cavitation by monitoring hydroxyl radical (OH) production on the thermolysis of H2O in the ultrasound field. In in vitro study, confocal microscopy was applied to detect the sub-cellular localization of PpIX in S180 cells before and after ultrasound exposure. Flow cytometry was used to detect the reactive oxygen species (ROS) generation during PpIX-SDT. MTT assay was performed to evaluate the cell viability of S180 cells after SDT treatment with or without ROS scavengers. The results show that PpIX displayed different spectral patterns in different solutions. PpIX was decomposed by ultrasound exposure as measured by the decreased absorption and fluorescence peak values in RPMI-1640 medium. In addition, the decomposition of PpIX was found to be simultaneously accompanied by OH production with increasing output power from ultrasound generator. PpIX at 1μg/ml significantly enhanced the ultrasound induced cavitation as measured by OH generation, and which was greatly eliminated by NaN3, histidine, mannitol, EDTA and catalase, but not by SOD. The in vitro study indicates more PpIX entered into S180 cells after ultrasound exposure. And, the extra-cellular PpIX play an important role in the enhanced cell killing of PpIX-SDT. SDT induced obvious ROS generation in S180 cells, which could be mostly inhibited by the general ROS scavenge NAC (N-acetylcysteine). Other scavengers such as NaN3, histidine, mannitol all partially prevented the SDT induced cell viability loss of S180 cells, suggesting OH, (1)O2 might be involved during the process. Copyright © 2012 Elsevier B.V. All rights reserved.

Nutritional geometry of calcium and phosphorus nutrition in broiler chicks. The effect of different dietary calcium and phosphorus concentrations and ratios on nutrient digestibility.

PubMed

Wilkinson, S J; Bradbury, E J; Thomson, P C; Bedford, M R; Cowieson, A J

2014-07-01

A total of 600 Ross 308-day-old male broiler chicks were used in a 28 day digestibility study to investigate the interaction between dietary calcium (Ca) and non-phytate phosphorus (nPP) on the digestibility of minerals and amino acids. Diets were formulated to be nutritionally adequate except for Ca and nPP. Fifteen mash diets based on corn and soya bean meal with varying concentrations of Ca (6.4 to 12.0 g/kg) and nPP (2.4 to 7.0 g/kg) were used. Diets were clustered around total densities of Ca and nPP of 12, 13.5 or 15.0 (g/kg) and within each density, a range of five Ca : nPP ratios (1.14 : 1, 1.5 : 1, 2.0 : 1, 2.75 : 1 and 4.0 : 1) were fed. Birds had free access to feed and water throughout the study. At day 28, birds were euthanised for the determination of apparent ileal mineral and amino acid digestibility. Data were modelled in R version 2.15 using a linear mixed-effects model and interrogation of the data was performed by fitting a low order polynomial function. At high Ca concentrations, increasing nPP led to an increase in the apparent digestibility of minerals. Apparent ileal digestibility of phosphorus (P) was enhanced with increasing dietary nPP up to 5.5 g/kg beyond which no improvements were found. Maximal Ca digestibility was found in diets with >8.0 g/kg Ca with concomitant low concentrations of nPP. Diets with a broader Ca : nPP ratio improved the digestibility of Ca but were deleterious to the digestibility of P. In this study, apparent digestibility of amino acids was broadly unaffected by dietary Ca and nPP concentrations. However, interactions between Ca and nPP were observed for the digestibility of glutamine, tyrosine and methionine (all P<0.001). Nitrogen digestibility showed discrete optima around 10.0 and 5.0 g/kg nPP and Na digestibility was maximised around 8 to 9.0 g/kg Ca and 4.5 to 5.4 g/kg nPP. These data show that the ratio of Ca : nPP is more influential to mineral digestibility than the absolute dietary concentration of each macro mineral.

Electromagnetic absorption behaviour of ferrite loaded three phase carbon fabric composites

NASA Astrophysics Data System (ADS)

Jagatheesan, Krishnasamy; Ramasamy, Alagirusamy; Das, Apurba; Basu, Ananjan

2018-02-01

This article investigates the electromagnetic absorption behaviours of carbon helical yarn fabric reinforced composites and manganese-zinc (Mn-Zn) ferrite particles loaded 3 phase fabric composites. A carbon helical yarn having stainless steel core was prepared and made into single jersey knitted fabric. The composite was prepared by sandwiching a fabric with polypropylene films and thermal pressed. The absorption values of helical yarn fabric composite was observed to be less in the C band region (4-8 GHz). For improving the absorption coefficients of composite, Mn-Zn ferrite particles were dispersed in the polypropylene (PP) composite. The ferrite loaded PP composites exhibited better permittivity and permeability values, hence the absorption loss of the composite was improved. The helical yarn fabric reinforced with Mn-Zn ferrite/PP composite showed larger absorption coefficients than virgin PP/fabric composite. The change in thermal stability and particle size distribution in the Mn-Zn ferrite/PP composite was also analyzed. At higher ferrite concentration, bimodal particle distribution was observed which increased the conductivity and shielding effectiveness (SE) of the composite. In addition, complex permittivity value was also increased for higher incident frequency (4-8 GHz). As the ferrite content increases, the dielectric loss and magnetic permeability of PP/ferrite increases due to increased magnetic loss. Hence, ferrite loaded PP composite showed the total SE of -14.2 dB with the absorption coefficients of 0.717. The S1C7 fabric composite having ferrite dispersion showed the better absorption loss and lower reflection coefficient of 14.2 dB and 0.345 respectively compared to virgin PP/helical yarn fabric composite. The increasing ferrite content (45 wt%) improved the absorption loss and total SE. Though, ferrite based fabric composite exhibits moderate absorptive shielding, it can be used as shielding panels in the electronic industries.

The Curves Exercise Suppresses Endotoxemia in Korean Women with Obesity.

PubMed

Jin, Seon Ah; Kim, Sun Kyeong; Seo, Hee Jung; Kim, Mijoo; Ahn, Kye Taek; Kim, Jun Hyung; Park, Jae Hyeong; Lee, Jae Hwan; Choi, Si Wan; Jeong, Jin Ok

2017-02-01

Obesity and metabolic syndrome is a worldwide pandemic and associated with high cardiovascular risk. Metabolic endotoxemia (ME) is thought to be an underlying molecular mechanism. It triggers toll-like receptor 4-mediated inflammatory adipokines and causes a chronic low grade inflammatory status, which results in cardiovascular risk increase. Exercise is the best nonpharmacological treatment to improve prognosis. In this study, we examined the circulating endotoxin level in Korean obese women and investigated effects of exercise on it. Women over body mass index (BMI) 25 kg/m² participated in a resistance training exercise, Curves. At baseline and after 12 weeks exercise, tests including blood samples were taken. In Korean obese women, the fasting endotoxin was 1.45 ± 0.11 EU/mL. Ingestion of a high calorie meal led to a peak level after 2 hours (postprandial 2 hours [PP2]) and a significant rise over the 4 hours (postprandial 4 hours [PP4]) in it (1.78 ± 0.15 and 1.75 ± 0.14 EU/mL for PP2 and PP4, P < 0.05 vs. fasting). After exercise, BMI and hip circumference were reduced significantly. The total cholesterol (TC) at fasting, PP2 and PP4 were decreased significantly. All levels of circulating endotoxin at fasting, PP2 and PP4 showed reduction. But, the peak change was only significant (baseline vs. 12 weeks for PP2; 1.78 ± 0.15 vs. 1.48 ± 0.06 EU/mL, P < 0.05). We report the circulating endotoxin level in Korean obese women for the first time. Also, we establish that energy intake leads to endotoxemia and exercise suppresses the peak endotoxemia after meal. It suggests an impact for a better prognosis in obese women who follow regular exercise.

Influence of verapamil on tachycardia-induced alterations of PP1 and PP2A in rabbit atrium

PubMed Central

Laszlo, Roman; Winkler, Christoph; Wöhrl, Stefan; Laszlo, Sara; Eick, Christian; Schreieck, Jürgen; Bosch, Ralph F

2007-01-01

BACKGROUND Long-term atrial fibrillation changes in many regulatory and structural processes may result in stabilization of the arrhythmia. There is evidence that decreased amplitude of L-type Ca2+ current – probably a key mechanism of atrial remodelling –resulting from changes in expression of regulatory proteins is at least jointly responsible. OBJECTIVES To assess the expressions of protein phosphatases PP1 and PP2A, as well as the effect of verapamil pretreatment (VPT), in the early phases of atrial fibrillation in a rabbit model. METHODS Four groups, each consisting of six animals, were studied: ‘not paced, no drug’ group; ‘paced, no drug’ group (rapid atrial pacing [RAP] 600 beats/min for 24 h); ‘not paced, verapamil’ (NPV) group (duration of VPT was seven days, verapamil 7.5 mg/kg was administered every 12 h); and ‘paced, verapamil’ (PV) group (pacemaker stimulation after VPT). Protein expression was evaluated by Western blot analysis. RESULTS RAP resulted in an augmented (32%) PP1 expression (not paced, no drug group versus paced, no drug group). The increase in PP1 expression was prevented with VPT (NPV group versus PV group). Expression of PP2A was not influenced by RAP. However, VPT led to an increase of PP2A expression (16%) after RAP (NPV group versus PV group). CONCLUSIONS Fortified expression of protein phosphatases might be – besides transcriptional downregulation of channel subunits – another important cause of reduced L-type Ca2+ current after RAP. Blocking L-type Ca2+ channels with verapamil to prevent tachycardia-induced changes of PP1 expression might be expedient. PMID:18651001

Synemin promotes AKT-dependent glioblastoma cell proliferation by antagonizing PP2A.

PubMed

Pitre, Aaron; Davis, Nathan; Paul, Madhumita; Orr, A Wayne; Skalli, Omar

2012-04-01

The intermediate filament protein synemin is present in astrocyte progenitors and glioblastoma cells but not in mature astrocytes. Here we demonstrate a role for synemin in enhancing glioblastoma cell proliferation and clonogenic survival, as synemin RNA interference decreased both behaviors by inducing G1 arrest along with Rb hypophosphorylation and increased protein levels of the G1/S inhibitors p21(Cip1) and p27(Kip1). Akt involvement was demonstrated by decreased phosphorylation of its substrate, p21(Cip1), and reduced Akt catalytic activity and phosphorylation at essential activation sites. Synemin silencing, however, did not affect the activities of PDPK1 and mTOR complex 2, which directly phosphorylate Akt activation sites, but instead enhanced the activity of the major regulator of Akt dephosphorylation, protein phosphatase type 2A (PP2A). This was accompanied by changes in PP2A subcellular distribution resulting in increased physical interactions between PP2A and Akt, as shown by proximity ligation assays (PLAs). PLAs and immunoprecipitation experiments further revealed that synemin and PP2A form a protein complex. In addition, treatment of synemin-silenced cells with the PP2A inhibitor cantharidic acid resulted in proliferation and pAkt and pRb levels similar to those of controls. Collectively these results indicate that synemin positively regulates glioblastoma cell proliferation by helping sequester PP2A away from Akt, thereby favoring Akt activation.

In vitro effect of 4-pentylphenol and 3-methyl-4-nitrophenol on murine splenic lymphocyte populations and cytokine/granzyme production.

PubMed

Yang, Lubing; Ma, Sihui; Wan, Yifang; Duan, Shuqi; Ye, Siyan; Du, Shengjie; Ruan, Xinwei; Sheng, Xia; Weng, Qiang; Taya, Kazuyoshi; Xu, Meiyu

2016-07-01

Gasoline exhaust particles (GEP) and diesel exhaust particles (DEP) are considered to be some of the most important air pollutants. Among the many constituents in these pollutant particles, 4-pentylphenol (PP) and 3-methyl-4-nitrophenol (PNMC) are considered important phenolics in GEP and DEP, respectively. The aim of this study was to investigate the effect of in vitro exposure to commercially-supplied PP and PNMC on populations of, and production of interleukin (IL)-2, IL-4 and granzyme-B by, mouse splenic lymphocytes. After in vitro exposure to PP or PNMC for 48 h, splenocyte viability was measured, cell phenotypes, e.g. B-cell (CD19), T-cells (CD3), T-cell subsets (CD4 and CD8), were quantified by flow cytometry and production of IL-2, IL-4 and granzyme-B was assessed via ELISA. The oxidative toxicity of PP and PNMC toward the splenocytes was also evaluated using measures of hydroxyl radical and malondiadehyde production and changes in glutathione peroxidase and superoxide dismutase activities. Results showed that in vitro exposure to PP and PNMC inhibited splenic cell parameters in a dose-related manner. Exposure to PP and PNMC decreased splenic T-lymphocyte populations and splenocyte production of cytokines and granzyme B, as well as induced oxidative stress in the splenocytes. The results also showed that the percentages of CD3(+) T-cells overall and of CD4(+) and CD8(+) T-cells therein, among exposed splenocytes, were reduced; neither compound appeared to affect levels of CD19(+) B-cells. Overall, the suppressive effects of PP were stronger than PNMC. The data here provide support for the proposal that PP-/PNMC-induced toxicity in splenocytes may be due at least in part to oxidative damage and that PP and PNMC - as components of GEP and DEP - might significantly impact on splenic T-cell formation/release of cytokines/granzymes in situ.

Evaluation of the immunogenicity and protective effects of a trivalent chimeric norovirus P particle immunogen displaying influenza HA2 from subtypes H1, H3 and B.

PubMed

Gong, Xin; Yin, He; Shi, Yuhua; He, Xiaoqiu; Yu, Yongjiao; Guan, Shanshan; Kuai, Ziyu; Haji, Nasteha M; Haji, Nafisa M; Kong, Wei; Shan, Yaming

2016-05-25

The ectodomain of the influenza A virus (IAV) hemagglutinin (HA) stem is highly conserved across strains and has shown promise as a universal influenza vaccine in a mouse model. In this study, potential B-cell epitopes were found through sequence alignment and epitope prediction in a stem fragment, HA2:90-105, which is highly conserved among virus subtypes H1, H3 and B. A norovirus (NoV) P particle platform was used to express the HA2:90-105 sequences from subtypes H1, H3 and B in loops 1, 2 and 3 of the protrusion (P) domain, respectively. Through mouse immunization and microneutralization assays, the immunogenicity and protective efficacy of the chimeric NoV P particle (trivalent HA2-PP) were tested against infection with three subtypes (H1N1, H3N2 and B) of IAV in Madin-Darby canine kidney cells. The protective efficacy of the trivalent HA2-PP was also evaluated preliminarily in vivo by virus challenge in the mouse model. The trivalent HA2-PP immunogen induced significant IgG antibody responses, which could be enhanced by a virus booster vaccination. Moreover, the trivalent HA2-PP immunogen also demonstrated in vitro neutralization of the H3 and B viruses, and in vivo protection against the H3 virus. Our results support the notion that a broadly protective vaccine approach using an HA2-based NoV P particle platform can provide cross-protection against challenge viruses of different IAV subtypes. The efficacy of the immunogen should be further enhanced for practicality, and a better understanding of the protective immune mechanism will be critical for the development of HA2-based multivalent vaccines.

Diversification of non-visual photopigment parapinopsin in spectral sensitivity for diverse pineal functions.

PubMed

Koyanagi, Mitsumasa; Wada, Seiji; Kawano-Yamashita, Emi; Hara, Yuichiro; Kuraku, Shigehiro; Kosaka, Shigeaki; Kawakami, Koichi; Tamotsu, Satoshi; Tsukamoto, Hisao; Shichida, Yoshinori; Terakita, Akihisa

2015-09-15

Recent genome projects of various animals have uncovered an unexpectedly large number of opsin genes, which encode protein moieties of photoreceptor molecules, in most animals. In visual systems, the biological meanings of this diversification are clear; multiple types of visual opsins with different spectral sensitivities are responsible for color vision. However, the significance of the diversification of non-visual opsins remains uncertain, in spite of the importance of understanding the molecular mechanism and evolution of varied non-visual photoreceptions. Here, we investigated the diversification of the pineal photopigment parapinopsin, which serves as the UV-sensitive photopigment for the pineal wavelength discrimination in the lamprey, linking it with other pineal photoreception. Spectroscopic analyses of the recombinant pigments of the two teleost parapinopsins PP1 and PP2 revealed that PP1 is a UV-sensitive pigment, similar to lamprey parapinopsin, but PP2 is a blue-sensitive pigment, with an absorption maximum at 460-480 nm, showing the diversification of non-visual pigment with respect to spectral sensitivity. We also found that PP1 and PP2 exhibit mutually exclusive expressions in the pineal organs of three teleost species. By using transgenic zebrafish in which these parapinopsin-expressing cells are labeled, we found that PP1-expressing cells basically possess neuronal processes, which is consistent with their involvement in wavelength discrimination. Interestingly, however, PP2-expressing cells rarely possess neuronal processes, raising the possibility that PP2 could be involved in non-neural responses rather than neural responses. Furthermore, we found that PP2-expressing cells contain serotonin and aanat2, the key enzyme involved in melatonin synthesis from serotonin, whereas PP1-expressing cells do not contain either, suggesting that blue-sensitive PP2 is instead involved in light-regulation of melatonin secretion. In this paper, we have clearly shown the different molecular properties of duplicated non-visual opsins by demonstrating the diversification of parapinopsin with respect to spectral sensitivity. Moreover, we have shown a plausible link between the diversification and its physiological impact by discovering a strong candidate for the underlying pigment in light-regulated melatonin secretion in zebrafish; the diversification could generate a new contribution of parapinopsin to pineal photoreception. Current findings could also provide an opportunity to understand the "color" preference of non-visual photoreception.

RRP1B Targets PP1 to Mammalian Cell Nucleoli and Is Associated with Pre-60S Ribosomal Subunits

PubMed Central

Chamousset, Delphine; De Wever, Veerle; Moorhead, Greg B.; Chen, Yan; Boisvert, Francois-Michel; Lamond, Angus I.

2010-01-01

A pool of protein phosphatase 1 (PP1) accumulates within nucleoli and accounts for a large fraction of the serine/threonine protein phosphatase activity in this subnuclear structure. Using a combination of fluorescence imaging with quantitative proteomics, we mapped the subnuclear localization of the three mammalian PP1 isoforms stably expressed as GFP-fusions in live cells and identified RRP1B as a novel nucleolar targeting subunit that shows a specificity for PP1β and PP1γ. RRP1B, one of two mammalian orthologues of the yeast Rrp1p protein, shows an RNAse-dependent localization to the granular component of the nucleolus and distributes in a similar manner throughout the cell cycle to proteins involved in later steps of rRNA processing. Quantitative proteomic analysis of complexes containing both RRP1B and PP1γ revealed enrichment of an overlapping subset of large (60S) ribosomal subunit proteins and pre-60S nonribosomal proteins involved in mid-late processing. Targeting of PP1 to this complex by RRP1B in mammalian cells is likely to contribute to modulation of ribosome biogenesis by mechanisms involving reversible phosphorylation events, thus playing a role in the rapid transduction of cellular signals that call for regulation of ribosome production in response to cellular stress and/or changes in growth conditions. PMID:20926688

Location of intense electromagnetic ion cyclotron (EMIC) wave events relative to the plasmapause: Van Allen Probes observations

NASA Astrophysics Data System (ADS)

Tetrick, S. S.; Engebretson, M. J.; Posch, J. L.; Olson, C. N.; Smith, C. W.; Denton, R. E.; Thaller, S. A.; Wygant, J. R.; Reeves, G. D.; MacDonald, E. A.; Fennell, J. F.

2017-04-01

We have studied the spatial location relative to the plasmapause (PP) of the most intense electromagnetic ion cyclotron (EMIC) waves observed on Van Allen Probes A and B during their first full precession in local time. Most of these waves occurred over an L range of from -1 to +2 RE relative to the PP. Very few events occurred only within 0.1 RE of the PP, and events with a width in L of < 0.2 RE occurred both inside and outside the PP. Wave occurrence was always associated with high densities of ring current ions; plasma density gradients or enhancements were associated with some events but were not dominant factors in determining the sites of wave generation. Storm main and recovery phase events in the dusk sector were often inside the PP, and dayside events during quiet times and compressions of the magnetosphere were more evenly distributed both inside and outside the PP. Superposed epoch analyses of the dependence of wave onset on solar wind dynamic pressure (Psw), the SME (SuperMAG auroral electrojet) index, and the SYM-H index showed that substorm injections and solar wind compressions were temporally closely associated with EMIC wave onset but to an extent that varied with frequency band, magnetic local time, and storm phase, and location relative to the PP. The fact that increases in SME and Psw were less strongly correlated with events at the PP than with other events might suggest that the occurrence of those events was affected by the density gradient.

The Role of C-SRC Activation in Prostate Tumor Progression

DTIC Science & Technology

2006-07-01

cancer cell line PANC -1 and prostrate cancer cell line PC-3 (B2-fold increase relative to control in both cell lines), while the Src inhibitory PP2 blocks...at normoxia in PANC -1 and PC-3 cells, its levels significantly increase in response to hypoxia (B4.5–8-fold induction). Inhibition of endo- genous c...Src activation in PANC -1 and PC-3 cells by PP2 drastically reduced HIF-1a levels to below those levels observed at normoxia (Figure 1a). STAT3 has

The PP4R1 sub-unit of protein phosphatase PP4 is essential for inhibition of NF-κB by merkel polyomavirus small tumour antigen.

PubMed

Abdul-Sada, Hussein; Müller, Marietta; Mehta, Rajni; Toth, Rachel; Arthur, J Simon C; Whitehouse, Adrian; Macdonald, Andrew

2017-04-11

Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with a high metastatic potential. The majority of MCC cases are caused by the Merkel cell polyomavirus (MCPyV), through expression of the virus-encoded tumour antigens. Whilst mechanisms attributing tumour antigen expression to transformation are being uncovered, little is known of the mechanisms by which MCPyV persists in the host. We previously identified the MCPyV small T antigen (tAg) as a novel inhibitor of nuclear factor kappa B (NF-kB) signalling and a modulator of the host anti-viral response. Here we demonstrate that regulation of NF-kB activation involves a previously undocumented interaction between tAg and regulatory sub-unit 1 of protein phosphatase 4 (PP4R1). Formation of a complex with PP4R1 and PP4c is required to bridge MCPyV tAg to the NEMO adaptor protein, allowing deactivation of the NF-kB pathway. Mutations in MCPyV tAg that fail to interact with components of this complex, or siRNA depletion of PP4R1, prevents tAg-mediated inhibition of NF-kB and pro-inflammatory cytokine production. Comparison of tAg binding partners from other human polyomavirus demonstrates that interactions with NEMO and PP4R1 are unique to MCPyV. Collectively, these data identify PP4R1 as a novel target for virus subversion of the host anti-viral response.

Inhibition of AMP Kinase by the Protein Phosphatase 2A Heterotrimer, PP2APpp2r2d*

PubMed Central

Joseph, Biny K.; Liu, Hsing-Yin; Francisco, Jamie; Pandya, Devanshi; Donigan, Melissa; Gallo-Ebert, Christina; Giordano, Caroline; Bata, Adam; Nickels, Joseph T.

2015-01-01

AMP kinase is a heterotrimeric serine/threonine protein kinase that regulates a number of metabolic processes, including lipid biosynthesis and metabolism. AMP kinase activity is regulated by phosphorylation, and the kinases involved have been uncovered. The particular phosphatases counteracting these kinases remain elusive. Here we discovered that the protein phosphatase 2A heterotrimer, PP2APpp2r2d, regulates the phosphorylation state of AMP kinase by dephosphorylating Thr-172, a residue that activates kinase activity when phosphorylated. Co-immunoprecipitation and co-localization studies indicated that PP2APpp2r2d directly interacted with AMP kinase. PP2APpp2r2d dephosphorylated Thr-172 in rat aortic and human vascular smooth muscle cells. A positive correlation existed between decreased phosphorylation, decreased acetyl-CoA carboxylase Acc1 phosphorylation, and sterol response element-binding protein 1c-dependent gene expression. PP2APpp2r2d protein expression was up-regulated in the aortas of mice fed a high fat diet, and the increased expression correlated with increased blood lipid levels. Finally, we found that the aortas of mice fed a high fat diet had decreased AMP kinase Thr-172 phosphorylation, and contained an Ampk-PP2APpp2r2d complex. Thus, PP2APpp2r2d may antagonize the aortic AMP kinase activity necessary for maintaining normal aortic lipid metabolism. Inhibiting PP2APpp2r2d or activating AMP kinase represents a potential pharmacological treatment for many lipid-related diseases. PMID:25694423

Impacts of dietary calcium, phytate, and nonphytate phosphorus concentrations in the presence or absence of phytase on inositol hexakisphosphate (IP6) degradation in different segments of broilers digestive tract

PubMed Central

Li, W.; Angel, R.; Kim, S.-W.; Brady, K.; Yu, S.; Plumstead, P. W.

2016-01-01

A total of 1,440 straight-run Heritage 56M × fast-feathering Cobb 500F broiler birds were fed from 11 to 13 d of age to determine the impacts of calcium (Ca), phytate phosphorus (PP), nonphytate P (nPP) and phytase concentrations on the myo-inositol hexakisphosphate (IP6) flow through the different parts of gastrointestinal tract (GIT). The experiment was a 2×2×2×3 randomized block design with 2 Ca (0.7 and 1.0%), 2 PP (0.23 and 0.34%), 2 nPP (0.28 and 0.45%) and 3 phytase (0-, 500-, and 1,000-phytase unit (FTU)/kg) concentrations. The experiment was replicated twice (block) with 3 replicates per treatment (Trt) of 10 birds per block. Concentration of IP6 in crop, proventriculus (Prov) plus (+) gizzard (Giz) and distal ileum digesta as well as the ileal IP6 disappearance was determined at 13 d of age. In crop, higher IP6 concentration was seen with increased Ca (P < 0.05). Despite the interaction between PP and phytase, higher dietary PP led to greater IP6 concentration (P < 0.05). Similar main effects of PP and phytase were also seen in Prov+Giz and ileum (P < 0.05) without interactions. Interaction between Ca and nPP on IP6 concentration was seen in Prov+Giz (P < 0.05). Decreased ileal IP6 disappearance was found at higher Ca (62.3% at 0.7% Ca vs. 57.5% at 1.0% Ca; P < 0.05). In general, adding phytase improved IP6 degradation but the degree of impact was dependent on nPP and PP (P < 0.05). In conclusion, phytase inclusion significantly reduced IP6 concentration and IP6 disappearance in distal ileum regardless of GIT segments or diet composition, but impacts of dietary Ca, nPP, and PP differed depending on GIT segment examined. PMID:26740131

Selective ablation of Ppp1cc gene in testicular germ cells causes oligo-teratozoospermia and infertility in mice.

PubMed

Sinha, Nilam; Puri, Pawan; Nairn, Angus C; Vijayaraghavan, Srinivasan

2013-11-01

The four isoforms of serine/threonine phosphoprotein phosphatase 1 (PP1), derived from three genes, are among the most conserved proteins known. The Ppp1cc gene encodes two alternatively spliced variants, PP1 gamma1 (PPP1CC1) and PP1 gamma2 (PPP1CC2). Global deletion of the Ppp1cc gene, which causes loss of both isoforms, results in male infertility due to impaired spermatogenesis. This phenotype was assumed to be due to the loss of PPP1CC2, which is abundant in testis. While PPP1CC2 is predominant, other PP1 isoforms are also expressed in testis. Given the significant homology between the four PP1 isoforms, the lack of compensation by the other PP1 isoforms for loss of one, only in testis, is surprising. Here we document, for the first time, expression patterns of the PP1 isoforms in postnatal developing and adult mouse testis. The timing and sites of testis expression of PPP1CC1 and PPP1CC2 in testis are nonoverlapping. PPP1CC2 is the only one of the four PP1 isoforms not detected in sertoli cells and spermatogonia. Conversely, PPP1CC2 may be the only PP1 isoform expressed in postmeiotic germ cells. Deletion of the Ppp1cc gene in germ cells at the differentiated spermatogonia stage of development and beyond in Stra8 promoter-driven Cre transgenic mice results in oligo-terato-asthenozoospermia and male infertility, thus phenocopying global Ppp1cc null (-/-) mice. Taken together, these results confirm that spermatogenic defects observed in the global Ppp1cc knockout mice and in mice expressing low levels of PPP1CC2 in testis are due to compromised functions of PPP1CC2 in meiotic and postmeiotic germ cells.

APPL1 Mediates Adiponectin-Induced LKB1 Cytosolic Localization Through the PP2A-PKCζ Signaling Pathway

PubMed Central

Deepa, Sathyaseelan S.; Zhou, Lijun; Ryu, Jiyoon; Wang, Changhua; Mao, Xuming; Li, Cai; Zhang, Ning; Musi, Nicolas; DeFronzo, Ralph A.; Liu, Feng

2011-01-01

We recently found that the adaptor protein containing pleckstrin homology domain, phosphotyrosine binding domain and leucine zipper motif (APPL)1 is essential for mediating adiponectin signal to induce liver kinase B (LKB)1 cytosloic translocation, an essential step for activation of AMP-activated protein kinase (AMPK) in cells. However, the underlying molecular mechanisms remain unknown. Here, we demonstrate that treating C2C12 myotubes with adiponectin promoted APPL1 interaction with protein phosphatase 2A (PP2A) and protein kinase Cζ (PKCζ), leading to the activation of PP2A and subsequent dephosphorylation and inactivation of PKCζ. The adiponectin-induced inactivation of PKCζ results in dephosphorylation of LKB1 at Ser307 and its subsequent translocation to the cytosol, where it stimulates AMPK activity. Interestingly, we found that metformin also induces LKB1 cytosolic translocation, but the stimulation is independent of APPL1 and the PP2A-PKCζ pathway. Together, our study uncovers a new mechanism underlying adiponectin-stimulated AMPK activation in muscle cells and shed light on potential targets for prevention and treatment of insulin resistance and its associated diseases. PMID:21835890

Differential dephosphorylation of the insulin receptor and its 160-kDa substrate (pp160) in rat adipocytes.

PubMed

Mooney, R A; Bordwell, K L

1992-07-15

A permeabilized rat adipocyte model was developed which permitted an examination of: 1) insulin receptor autophosphorylation, 2) phosphorylation of a putative insulin receptor substrate of 160 kDa, pp160, and 3) the dephosphorylation reactions associated with each of these phosphoproteins. Rat adipocytes, preincubated with [32P]orthophosphate for 2 h, were exposed to insulin (10(-7) M) at the time of digitonin permeabilization. Phosphorylation of pp160 and autophosphorylation of the insulin receptor increased as a function of Mn2+ concentration in the media with near maximum responses at 10 mM. Maximum response was at least as large as the intact cell response to 10(-7) M insulin. In contrast, magnesium did not increase phosphorylation of pp160 although an increase in receptor autophosphorylation was observed. Autophosphorylation was preserved at digitonin concentrations of 20-100 micrograms/ml, but pp160 phosphorylation was negligible beyond 40 micrograms/ml. Our previous work demonstrated that the insulin receptor was associated with a phosphotyrosine phosphatase activity in permeabilized adipocytes (Mooney, R., and Anderson, D. (1989) J. Biol. Chem. 264, 6850-6857). The current permeabilized adipocyte model made possible an examination of the effects of phosphotyrosine phosphatase inhibitors, including several divalent metal cations (Zn2+, Co2+, and Ni2+), vanadate, and molybdate on both net phosphorylation of pp160 and autophosphorylation of the insulin receptor. Zn2+ at 100 microM, Ni2+ at 1 mM, and Co2+ at 1 or 5 mM increased insulin-dependent phosphorylation of pp160 at least 5-fold and autophosphorylation 2-fold. At higher concentrations of Zn2+ (1 mM) and Ni2+ (5 mM), however, no increase in phosphorylation of pp160 was observed and autophosphorylation was inhibited. Vanadate (1 mM) and molybdate (100 microM) increased insulin-dependent phosphorylation of pp160 by 3-fold when tested separately and 7-fold in combination. Insulin receptor autophosphorylation was increased 50% by each and 3-fold when the agents were combined. Dephosphorylation of pp160 and the insulin receptor was analyzed directly by permeabilizing prelabeled insulin-treated adipocytes in the presence of EDTA (10 mM). Dephosphorylation of pp160 was especially rapid with a t1/2 of approximately 10 s. The t1/2 for the insulin receptor was 37 s. Zn2+ at 1 mM (a concentration that inhibited the insulin receptor kinase) was a strong inhibitor of dephosphorylation, prolonging the rate of pp160 dephosphorylation more than 12-fold and insulin receptor dephosphorylation 3-fold.(ABSTRACT TRUNCATED AT 400 WORDS)

Zinc protoporphyrin inhibition of lipopolysaccharide-, lipoteichoic acid-, and peptidoglycan-induced nitric oxide production through stimulating iNOS protein ubiquitination.

PubMed

Chow, Jyh-Ming; Lin, Hui-Yi; Shen, Shing-Chuan; Wu, Ming-Shun; Lin, Cheng-Wei; Chiu, Wen-Ta; Lin, Chien-Huang; Chen, Yen-Chou

2009-06-15

In the present study, zinc protoporphyrin (ZnPP), but not ferric protoporphyrin (FePP), tin protoporphyrin (SnPP), or zinc chloride (ZnCl(2)), at the doses of 0.5, 1, and 2 microM, dose-dependently inhibited lipopolysaccharide- (LPS), lipoteichoic acid (LTA), and peptidoglycan (PGN)-induced inducible nitric oxide (iNOS) and nitric oxide (NO) production with an increase in heme oxygenase 1 (HO-1) protein in RAW264.7 macrophages in a serum-free condition. NO inhibition and HO-1 induction by ZnPP were blocked by the separate addition of fetal bovine serum (FBS) and bovine serum albumin (BSA). A decrease in the iNOS/NO ratio and an increase in HO-1 protein by ZnPP were identified in three different conditions including ZnPP pretreatment, ZnPP co-treatment, and ZnPP post-treatment with LPS and LTA. Activation of c-Jun N-terminal kinases (JNKs) and extracellular regulated kinases (ERKs) were detected in LPS-, LTA-, and PGN-treated RAW264.7 cells, and iNOS/NO production was blocked by adding the JNK inhibitor, SP600125, but not the ERK inhibitor, PD98059. However, ZnPP addition potentiated ERK and JNK protein phosphorylation stimulated by LPS, LTA, and PGN. Increases in total protein ubiquitination and ubiquitinated iNOS proteins were detected in ZnPP-treated macrophages elicited by LPS according to Western and immunoprecipitation/Western blotting assays, respectively. The decrease in LPS-induced iNOS protein by ZnPP was reversed by adding the proteasome inhibitors MG132 and lactacystin. The reduction in HO-1 protein induced by ZnPP via transfection of HO-1 small interfering RNA did not affect the inhibitory effect of ZnPP against LPS-induced iNOS/NO production and protein ubiquitination induced by ZnPP in macrophages. Data of the present study provide the first evidence to support ZnPP effectively inhibiting inflammatory iNOS/NO production through activation of protein ubiquitination in a HO-1-independent manner in macrophages.

Zinc protoporphyrin inhibition of lipopolysaccharide-, lipoteichoic acid-, and peptidoglycan-induced nitric oxide production through stimulating iNOS protein ubiquitination

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chow, J.-M.; Lin, H.-Y.; Shen, S.-C.

2009-06-15

In the present study, zinc protoporphyrin (ZnPP), but not ferric protoporphyrin (FePP), tin protoporphyrin (SnPP), or zinc chloride (ZnCl{sub 2}), at the doses of 0.5, 1, and 2 {mu}M, dose-dependently inhibited lipopolysaccharide- (LPS), lipoteichoic acid (LTA), and peptidoglycan (PGN)-induced inducible nitric oxide (iNOS) and nitric oxide (NO) production with an increase in heme oxygenase 1 (HO-1) protein in RAW264.7 macrophages in a serum-free condition. NO inhibition and HO-1 induction by ZnPP were blocked by the separate addition of fetal bovine serum (FBS) and bovine serum albumin (BSA). A decrease in the iNOS/NO ratio and an increase in HO-1 protein bymore » ZnPP were identified in three different conditions including ZnPP pretreatment, ZnPP co-treatment, and ZnPP post-treatment with LPS and LTA. Activation of c-Jun N-terminal kinases (JNKs) and extracellular regulated kinases (ERKs) were detected in LPS-, LTA-, and PGN-treated RAW264.7 cells, and iNOS/NO production was blocked by adding the JNK inhibitor, SP600125, but not the ERK inhibitor, PD98059. However, ZnPP addition potentiated ERK and JNK protein phosphorylation stimulated by LPS, LTA, and PGN. Increases in total protein ubiquitination and ubiquitinated iNOS proteins were detected in ZnPP-treated macrophages elicited by LPS according to Western and immunoprecipitation/Western blotting assays, respectively. The decrease in LPS-induced iNOS protein by ZnPP was reversed by adding the proteasome inhibitors MG132 and lactacystin. The reduction in HO-1 protein induced by ZnPP via transfection of HO-1 small interfering RNA did not affect the inhibitory effect of ZnPP against LPS-induced iNOS/NO production and protein ubiquitination induced by ZnPP in macrophages. Data of the present study provide the first evidence to support ZnPP effectively inhibiting inflammatory iNOS/NO production through activation of protein ubiquitination in a HO-1-independent manner in macrophages.« less

Two highly-related regulatory subunits of PP2A exert opposite effects on TGF-β/Activin/Nodal signalling

PubMed Central

Batut, Julie; Schmierer, Bernhard; Cao, Jing; Raftery, Laurel A.; Hill, Caroline S.; Howell, Michael

2016-01-01

Summary We identify Bα (PPP2R2A) and Bδ (PPP2R2D), two highly-related members of the B family of regulatory subunits of the protein phosphatase PP2A, as important modulators of TGF-β/Activin/Nodal signalling, which affect the pathway in opposite ways. Knockdown of Bα in Xenopus embryos or mammalian tissue culture cells suppresses TGF-β/Activin/Nodal-dependent responses, whereas knockdown of Bδ enhances these responses. Moreover, in Drosophila, overexpression of Smad2 rescues a severe wing phenotype caused by overexpression of the single Drosophila PP2A B subunit, Twins. We show that in vertebrates Bα enhances TGF-β/Activin/Nodal signalling by stabilising the basal levels of type I receptor, whereas Bδ negatively modulates these pathways by restricting receptor activity. Thus, these highly-related members of the same subfamily of PP2A regulatory subunits differentially regulate TGF-β/Activin/Nodal signalling to elicit opposing biological outcomes. PMID:18697906

Measurement of Υ(1S + 2S +3S) production in p + p and Au + Au collisions at \\(\\sqrt{s_{\\mathrm{NN}}}=200\\) GeV

DOE PAGES

Adare, A.; Afanasiev, S.; Aidala, C.; ...

2015-02-24

Measurements of bottomonium production in heavy-ion and p+p collisions at the Relativistic Heavy Ion Collider (RHIC) are presented. The inclusive yield of the three Υ states, Υ(1S + 2S + 3S), was measured in the PHENIX experiment via electron-positron decay pairs at midrapidity for Au+Au and p+p collisions at \\(\\sqrt{s_{\\mathrm{NN}}}=200\\) GeV. The Υ(1S + 2S + 3S) → e⁺e⁻ differential cross section at midrapidity was found to be B eedσ/dy = 108 ± 38 (stat) ± 15 (syst) ± 11 (luminosity) pb in p+p collisions. The nuclear modification factor in the 30% most central Au+Au collisions indicates a suppression ofmore » the total Υ state yield relative to the extrapolation from p+p collision data. Thus, the suppression is consistent with measurements at higher energies by the CMS experiment at the Large Hadron Collider.« less

Tuneable reactivity with PPh3 and SnX2 of four- and five-coordinate Pd(II) and Pt(II) complexes containing polyphosphines.

PubMed

Fernández-Anca, Damián; García-Seijo, M Inés; García-Fernández, M Esther

2013-07-28

The reactivity of the unusual d(8) trigonal-bipyramidal systems [MX(PP3)]X (X = Cl: M = Pd(1a), Pt(2a); X = Br: M = Pd(3a), Pt(4a); X = I: M = Pd(5a), Pt(6a); PP3 = tris[2-(diphenylphosphino)ethyl]phosphine) in CHCl3-CH3OH, the square-pyramidal compounds [MCl(NP3)]Cl (M = Pd(7a); Pt(8a); NP3 = tris[2-(diphenylphosphino)ethyl]amine) in CD3OD-DMF and the distorted square-planar mononuclear [MX(PNP)]X (M = Pd: X = Cl(10a); M = Pt: X = I(10b); PNP = bis[2-(diphenylphosphino)ethyl]amine) and the heteronuclear [PdAu2X4(PP3)] [X = I(9a), Cl(14a), Br(15a)] and [MAuX2(PP3)]X [M = Pd: X = Cl(16a); M = Pt: X = Cl(17a), Br(18a)] species in CDCl3 with PPh3 + SnX2 has been explored to establish the factors that influence the nature of the products. With the mononuclear precursors the course of the reaction is strongly dependent on the tripodal or linear arrangement of the polydentate ligand and in the former case on the halogen. Thus, while for chlorides (1a-2a, 7a-8a) and bromides (3a-4a) the reaction led to the trigonal-bipyramidal compounds [M(SnCl3)(AP3)][SnCl3] [A = P: M = Pd(1), Pt(2); A = N: M = Pd(7), Pt(8)], [MBr(PP3)][SnBr3] [M = Pd(4), Pt(6)] containing M-Sn and M-Br bonds, respectively, for iodides (5a-6a) resulted in the unknown neutral square-planar compounds [MI2(PP(PO)2)(SnI2)2] [M = Pd(9) and Pt(10)] bearing two dangling P=O-SnI2 units and P2MI2 environments. However, complexes of the type [PtCl(PP2PO)X]X' [X = SnCl2, X' = [SnCl3](-)(11)] and [M(PP(PO)2)2X4]X'2 [X = SnCl2, X' = [SnCl3](-): M = Pd(12), Pt(13)] showing P=O-SnCl2 arms were obtained by direct reaction of [PtCl(PP2PO)]Cl (11a) and [M(PP(PO)2)2]Cl2 [M = Pd(12a), Pt(13a)] with SnCl2 in CH3OH. Although complex 9 was also prepared by interaction of the heteronuclear iodide 9a with PPh3 + SnI2 in CDCl3, the use of the neutral and ionic heteronuclear chlorides and bromides (14a-18a) as starting materials afforded the distorted square-planar ionic systems [MAuX'(PP3)(PPh3)][SnX3]2 [M = Pd: X = Cl, X' = SnCl3(-)(14); X = Br, X' = SnBr3(-)(15); M = Pt: X = Cl, X' = SnCl3(-)(17); X = Br, X' = SnBr3(-)(18)] containing M-SnX3 and P-Au-PPh3 functionalities. It was found that these reactions where the heteronuclear species are the precursors proceed via the trigonal-bipyramidal halides not only with X = Cl and Br(1a-4a) but also I(5a). When the precursors were 10a and 10b the reaction occurred with formation of [Pd(PNP)(PPh3)][SnCl3]2 (23) and [Pt(PNP)(PPh3)][SnCl2I]2 (24) showing M-PPh3 units and trihalostannato counter anions.

Measurement of the ratio of differential cross sections σ(pp̄→Z+b jet)/σ(pp̄→Z+jet) in pp̄ collisions at √s=1.96 TeV

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abazov, V. M.; Abbott, B.; Acharya, B. S.

2013-05-28

We measure the ratio of cross sections, σ(pp̄→Z+b jet)/σ(pp̄→Z+jet), for associated production of a Z boson with at least one jet. The ratio is also measured as a function of the Z boson transverse momentum, jet transverse momentum, jet pseudorapidity, and the azimuthal angle between the Z boson with respect to the highest p T b tagged jet. These measurements use data collected by the D0 experiment in Run II of Fermilab’s Tevatron pp̄ Collider at a center-of-mass energy of 1.96 TeV, and correspond to an integrated luminosity of 9.7 fb⁻¹. The results are compared to predictions from next-to-leading ordermore » calculations and various Monte Carlo event generators.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adare, A.; Afanasiev, S.; Aidala, C.

Measurements of bottomonium production in heavy-ion and p+p collisions at the Relativistic Heavy Ion Collider (RHIC) are presented. The inclusive yield of the three Υ states, Υ(1S + 2S + 3S), was measured in the PHENIX experiment via electron-positron decay pairs at midrapidity for Au+Au and p+p collisions at \\(\\sqrt{s_{\\mathrm{NN}}}=200\\) GeV. The Υ(1S + 2S + 3S) → e⁺e⁻ differential cross section at midrapidity was found to be B eedσ/dy = 108 ± 38 (stat) ± 15 (syst) ± 11 (luminosity) pb in p+p collisions. The nuclear modification factor in the 30% most central Au+Au collisions indicates a suppression ofmore » the total Υ state yield relative to the extrapolation from p+p collision data. Thus, the suppression is consistent with measurements at higher energies by the CMS experiment at the Large Hadron Collider.« less

Measurement of the production and muonic decay rate of W and Z bosons in pp¯ collisions at √s =1.8 TeV

NASA Astrophysics Data System (ADS)

Abe, F.; Amidei, D.; Apollinari, G.; Atac, M.; Auchincloss, P.; Baden, A. R.; Bacchetta, N.; Bailey, M. W.; Bamberger, A.; de Barbaro, P.; Barnett, B. A.; Barbaro-Galtieri, A.; Barnes, V. E.; Baumann, T.; Bedeschi, F.; Behrends, S.; Belforte, S.; Bellettini, G.; Bellinger, J.; Benjamin, D.; Bensinger, J.; Beretvas, A.; Berge, J. P.; Bertolucci, S.; Bhadra, S.; Binkley, M.; Bisello, D.; Blair, R.; Blocker, C.; Bodek, A.; Bolognesi, V.; Booth, A. W.; Boswell, C.; Brandenburg, G.; Brown, D.; Buckley-Geer, E.; Budd, H. S.; Busetto, G.; Byon-Wagner, A.; Byrum, K. L.; Campagnari, C.; Campbell, M.; Caner, A.; Carey, R.; Carithers, W.; Carlsmith, D.; Carroll, J. T.; Cashmore, R.; Castro, A.; Cervelli, F.; Chadwick, K.; Chiarelli, G.; Chinowsky, W.; Cihangir, S.; Clark, A. G.; Cobal, M.; Connor, D.; Contreras, M.; Cooper, J.; Cordelli, M.; Crane, D.; Curatolo, M.; Day, C.; Dejongh, F.; dell'agnello, S.; dell'orso, M.; Demortier, L.; Denby, B.; Derwent, P. F.; Devlin, T.; Dibitonto, D.; Dickson, M.; Drucker, R. B.; Einsweiler, K.; Elias, J. E.; Ely, R.; Eno, S.; Errede, S.; Esposito, B.; Etchegoyen, A.; Flaugher, B.; Foster, G. W.; Franklin, M.; Freeman, J.; Frisch, H.; Fuess, T.; Fukui, Y.; Garfinkel, A. F.; Gauthier, A.; Geer, S.; Gerdes, D. W.; Giannetti, P.; Giokaris, N.; Giromini, P.; Gladney, L.; Gold, M.; Goulianos, K.; Grassmann, H.; Grieco, G. M.; Grosso-Pilcher, C.; Haber, C.; Hahn, S. R.; Handler, R.; Hara, K.; Harral, B.; Harris, R. M.; Hauser, J.; Hawk, C.; Hessing, T.; Hollebeek, R.; Holloway, L.; Hu, P.; Hubbard, B.; Huffman, B. T.; Hughes, R.; Hurst, P.; Huth, J.; Hylen, J.; Incagli, M.; Ino, T.; Iso, H.; Jensen, H.; Jessop, C. P.; Johnson, R. P.; Joshi, U.; Kadel, R. W.; Kamon, T.; Kanda, S.; Kardelis, D. A.; Karliner, I.; Kearns, E.; Keeble, L.; Kephart, R.; Kesten, P.; Keup, R. M.; Keutelian, H.; Kim, D.; Kim, S.; Kim, Y. K.; Kirsch, L.; Kondo, K.; Konigsberg, J.; Kovacs, E.; Kuhlmann, S. E.; Kuns, E.; Laasanen, A. T.; Lamoureux, J. I.; Leone, S.; Lewis, J.; Li, W.; Limon, P.; Liss, T. M.; Lockyer, N.; Loreti, M.; Low, E. H.; Luchini, C. B.; Lukens, P.; Maas, P.; Maeshima, K.; Mangano, M.; Marriner, J. P.; Mariotti, M.; Markeloff, R.; Markosky, L. A.; Mattingly, R.; McIntyre, P.; Menzione, A.; Meyer, T.; Mikamo, S.; Miller, M.; Mimashi, T.; Miscetti, S.; Mishina, M.; Miyashita, S.; Morita, Y.; Moulding, S.; Mueller, J.; Mukherjee, A.; Nakae, L. F.; Nakano, I.; Nelson, C.; Newman-Holmes, C.; Ng, J. S.; Ninomiya, M.; Nodulman, L.; Ogawa, S.; Paoletti, R.; Papadimitriou, V.; Para, A.; Pare, E.; Park, S.; Patrick, J.; Pauletta, G.; Pescara, L.; Phillips, T. J.; Ptohos, F.; Plunkett, R.; Pondrom, L.; Proudfoot, J.; Punzi, G.; Quarrie, D.; Ragan, K.; Redlinger, G.; Rhoades, J.; Roach, M.; Rimondi, F.; Ristori, L.; Rodrigo, T.; Rohaly, T.; Roodman, A.; Sakumoto, W. K.; Sansoni, A.; Sard, R. D.; Savoy-Navarro, A.; Scarpine, V.; Schlabach, P.; Schmidt, E. E.; Schneider, O.; Schub, M. H.; Schwitters, R.; Scribano, A.; Segler, S.; Seiya, Y.; Shapiro, M.; Shaw, N. M.; Sheaff, M.; Shochet, M.; Siegrist, J.; Sinervo, P.; Skarha, J.; Sliwa, K.; Smith, D. A.; Snider, F. D.; Song, L.; Spahn, M.; Sphicas, P.; St. Denis, R.; Stefanini, A.; Sullivan, G.; Swartz, R. L.; Takano, M.; Tartarelli, F.; Takikawa, K.; Tarem, S.; Theriot, D.; Timko, M.; Tipton, P.; Tkaczyk, S.; Tollestrup, A.; Tonnison, J.; Trischuk, W.; Turini, N.; Tsay, Y.; Ukegawa, F.; Underwood, D.; Vejcik, S.; Vidal, R.; Wagner, R. G.; Wagner, R. L.; Wainer, N.; Walsh, J.; Watts, T.; Webb, R.; Wendt, C.; Wenzel, H.; Wester, W. C.; Westhusing, T.; White, S. N.; Wicklund, A. B.; Williams, H. H.; Winer, B. L.; Wyss, J.; Yagil, A.; Yasuoka, K.; Yeh, G. P.; Yoh, J.; Yokoyama, M.; Yun, J. C.; Zanetti, A.; Zetti, F.; Zucchelli, S.

1992-07-01

An analysis of proton-antiproton collisions at √s =1.8 TeV recorded with the Collider Detector at Fermilab (CDF) yields σ(pp¯-->WX)B(W-->μν)=2.21+/-0.22 nb and σ(pp¯-->ZX)B(Z -->μ+μ-)=0.226+/-0.032 nb. The ratio is Rμ=σWB(W-->μν)/σZB(Z-->μ+μ-)=9.8+/-1.2. Combining with previous CDF electron results gives σWB(W-->lν)=2.20+/-0.20 nb, σZB(Z-->l+l-)=0.214+/-0.023 nb, and Rl=10.0+/-0.8. We extract the ratios of the coupling constants gμ/ge and gτ/gμ. Using standard model assumptions we deduce the inverse branching ratio B-1(W-->lν), the width Γ(W), and a decay-mode-independent lower bound on the top quark mass of 45 GeV/c2 (95% C.L.).

Identification and elucidation of in vivo function of two alanine racemases from Pseudomonas putida KT2440.

PubMed

Duque, Estrella; Daddaoua, Abdelali; Cordero, Baldo F; De la Torre, Jesús; Antonia Molina-Henares, Maria; Ramos, Juan-Luis

2017-10-01

The genome of Pseudomonas putida KT2440 contains two open reading frames (ORFs), PP_3722 and PP_5269, that encode proteins with a Pyridoxal phosphate binding motif and a high similarity to alanine racemases. Alanine racemases play a key role in the biosynthesis of D-alanine, a crucial amino acid in the peptidoglycan layer. For these ORFs, we generated single and double mutants and found that inactivation of PP_5269 resulted in D-alanine auxotrophy, while inactivation of PP_3722 did not. Furthermore, as expected, the PP_3722/PP_5269 double mutant was a strict auxotroph for D-alanine. These results indicate that PP_5269 is an alr allele and that it is the essential alanine racemase in P. putida. We observed that the PP_5269 mutant grew very slowly, while the double PP_5269/PP_3722 mutant did not grow at all. This suggests that PP_3722 may replace PP_5269 in vivo. In fact, when the ORF encoding PP_3772 was cloned into a wide host range expression vector, ORF PP_3722 successfully complemented P. putida PP_5269 mutants. We purified both proteins to homogeneity and while they exhibit similar K M values, the V max of PP_5269 is fourfold higher than that of PP_3722. Here, we propose that PP_5269 and PP_3722 encode functional alanine racemases and that these genes be named alr-1 and alr-2 respectively. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

Polypharmacy and Unplanned Hospitalizations in Patients with Rheumatoid Arthritis.

PubMed

Filkova, Maria; Carvalho, João; Norton, Sam; Scott, David; Mant, Tim; Molokhia, Mariam; Cope, Andrew; Galloway, James

2017-12-01

Polypharmacy (PP), the prescribing of multiple drugs for an individual, is rising in prevalence. PP associates with an increased risk of adverse drug reactions (ADR) and hospital admissions. We investigated the relationship between PP, characteristics of rheumatoid arthritis (RA), and the risk of unplanned hospital admissions. Patients from a hospital RA cohort were retrospectively analyzed. Information was collected from electronic medical records. Cox proportional hazards were used to compare hospitalization risk according to levels of PP. Admissions were adjudicated to determine whether an ADR was implicated. The study included 1101 patients; the mean number of all medications was 5. PP correlated with increasing age, disease duration, disease activity, and disability. At least 1 unplanned admission occurred for 16% of patients. Patients taking ≥ 10 medications had an adjusted HR for hospitalization of 3.1 (95% CI 2.1-4.5), compared to those taking 0-5 medications. Corticosteroid use associated with a doubling in adjusted risk of admission of 1.7 (95% CI 1.2-2.4). The most common reason for hospitalization was infection (28%). While in half of all admissions an ADR was a possible contributing factor, only 2% of admissions were found to directly result from an ADR. PP is common in RA and is a prognostic marker associated with increased risk of acute hospitalizations. Our data suggest that PP may be an indicator of comorbidity burden rather than a contributing cause of a drug-related toxicity. PP should be monitored to minimize inappropriate combination of prescribed medications. PP may be a useful predictor of clinical outcomes in epidemiologic studies.

Homemade-device-induced negative pressure promotes wound healing more efficiently than VSD-induced positive pressure by regulating inflammation, proliferation and remodeling.

PubMed

Liu, Jinyan; Hu, Feng; Tang, Jintian; Tang, Shijie; Xia, Kun; Wu, Song; Yin, Chaoqi; Wang, Shaohua; He, Quanyong; Xie, Huiqing; Zhou, Jianda

2017-04-01

Vacuum sealing drainage (VSD) is an effective technique used to promote wound healing. However, recent studies have shown that it exerts positive pressure (PP) rather than negative pressure (NP) on skin. In this study, we created a homemade device that could maintain NP on the wound, and compared the therapeutic effects of VSD-induced PP to those of our homemade device which induced NP on wound healing. The NP induced by our device required less time for wound healing and decreased the wound area more efficiently than the PP induced by VSD. NP and PP both promoted the inflammatory response by upregulating neutrophil infiltration and interleukin (IL)‑1β expression, and downregulating IL‑10 expression. Higher levels of epidermal growth factor (EGF), transforming growth factor (TGF)‑β and platelet-derived growth factor (PDGF), and lower levels of basic fibroblast growth factor (bFGF) were observed in the wound tissue treated with NP compared to the wound tissue exposed to PP. Proliferation in the wound tissue exposed to NP on day 10 was significantly higher than that in wound tissue exposed to PP. NP generated more fibroblasts, keratinized stratified epithelium, and less epithelia with stemness than PP. The levels of ccollagen Ⅰ and Ⅲ were both decreased in both the NP and PP groups. NP induced a statistically significant increase in the expression of fibronectin (FN) on days 3 and 10 compared to PP. Furthermore, the level of matrix metalloproteinase (MMP)‑13 increased in the NP group, but decreased in the PP group on day 3. NP also induced a decrease in the levels of tissue inhibitor of metalloproteinase (TIMP)‑1 and TIMP‑2 during the early stages of wound healing, which was significantly different from the increasing effect of PP on TIMP‑1 and TIMP‑2 levels at the corresponding time points. On the whole, our data indicate that our homemade device which induced NP, was more efficient than VSD‑induced PP on wound healing by regulating inflammation, secretion, proliferation and the distribution of different cells in wound tissue.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bahig, Houda; Simard, Dany; Létourneau, Laurent

Purpose: To determine the incidence of pseudoprogression (PP) after spine stereotactic body radiation therapy based on a detailed and quantitative assessment of magnetic resonance imaging (MRI) morphologic tumor alterations, and to identify predictive factors distinguishing PP from local recurrence (LR). Methods and Materials: A retrospective analysis of 35 patients with 49 spinal segments treated with spine stereotactic body radiation therapy, from 2009 to 2014, was conducted. The median number of follow-up MRI studies was 4 (range, 2-7). The gross tumor volumes (GTVs) within each of the 49 spinal segments were contoured on the pretreatment and each subsequent follow-up T1- andmore » T2-weighted MRI sagittal sequence. T2 signal intensity was reported as the mean intensity of voxels constituting each volume. LR was defined as persistent GTV enlargement on ≥2 serial MRI studies for ≥6 months or on pathologic confirmation. PP was defined as a GTV enlargement followed by stability or regression on subsequent imaging within 6 months. Kaplan-Meier analysis was used for estimation of actuarial local control, disease-free survival, and overall survival. Results: The median follow-up was 23 months (range, 1-39 months). PP was identified in 18% of treated segments (9 of 49) and LR in 29% (14 of 49). Earlier volume enlargement (5 months for PP vs 15 months for LR, P=.005), greater GTV to reference nonirradiated vertebral body T2 intensity ratio (+30% for PP vs −10% for LR, P=.005), and growth confined to 80% of the prescription isodose line (80% IDL) (8 of 9 PP cases vs 1 of 14 LR cases, P=.002) were associated with PP on univariate analysis. Multivariate analysis confirmed an earlier time to volume enlargement and growth within the 80% IDL as significant predictors of PP. LR involved the epidural space in all but 1 lesion, whereas PP was confined to the vertebral body in 7 of 9 cases. Conclusions: PP was observed in 18% of treated spinal segments. Tumor growth confined to the 80% IDL and earlier time to tumor enlargement were predictive for PP.« less

Effect of cyclical thermal to mechanical properties of Hybrid Laminate Composites (HLC) with skin recycle polypropylene/natural fiber/halloysite and core PP/KF composites

NASA Astrophysics Data System (ADS)

Sri Suharty, Neng; Ismail, Hanafi; Suci Handayani, Desi; Diharjo, Kuncoro; Rachman Wibowo, Fajar; Arnita Wuri, Margaretha

2016-02-01

This research has successfully synthesized six hybrid laminate composites (HLC). These HLC consist of two layers skin composites and one layer of core PP/KF composites. There are sticked with epoxy adhesive by using cold press method. In this research 6 types of skin are used, namely the rPP (recycled polypropylene, HC1); rPP/DVB/PP-g-AA/KF (HC2); rPP/DVB/PP-g-AA/Hall (HC3); rPP/DVB/PP-g-AA/Hall+ZB (HC4); rPP/DVB/PP-g-AA/KF/Hall (HC5) and rPP/DVB/PP-g-AA/KF/Hall+ZB (HC6) composites. The mechanical properties assessment tensile strength (TS) of various HLC before and after cyclical thermal (CT) was done by ASTM D638. While testing the flame retardant: such as time to ignition (TTI) and burning rate (BR) was done by ASTM D635. Heat stability of HLC can be recognized by conducting the CT treatment. It is to determine the effect of fluctuating heat loads on mechanical properties of HLC materials. The TS result of five HLCs (HC2, HC3, HC4, HC5 and HC6) before CT treatment were higher than HC1 (blank HLC). Those five HLC are also able to increase the TTI and reduce the BR compared to HC1. The CT treatment conditions performed at 45 oC as much as 125 times. After CT treatment, the TS values only slightly decline compared to before CT treatment.

Optimized enzyme-linked immunosorbent assay for detecting cytomegalovirus infections during clinical trials of recombinant vaccines.

PubMed

Pagnon, Anke; Piras, Fabienne; Gimenez-Fourage, Sophie; Dubayle, Joseline; Arnaud-Barbe, Nadège; Hessler, Catherine; Caillet, Catherine

2017-11-01

In clinical trials of cytomegalovirus (CMV) glycoprotein B (gB) vaccines, CMV infection is detected by first depleting serum of anti-gB antibodies and then measuring anti-CMV antibodies with a commercially available enzyme-linked immunosorbent assay (ELISA) kit, with confirmation of positive findings by immunoblot. Identification of CMV immunoantigens for the development of an ELISA that detects specifically CMV infection in clinical samples from individuals immunized with gB vaccines. Sensitivity and specificity of ELISAs using antigenic regions of CMV proteins UL83/pp65, UL99/pp28, UL44/pp52, UL80a/pp38, UL57, and UL32/pp150 were measured. An IgG ELISA using a UL32/pp150 [862-1048] capture peptide was the most specific (93.7%) and sensitive (96.4%) for detecting CMV-specific antibodies in sera. The ELISA successfully detected CMV-specific antibodies in 22 of 22 sera of subjects who had been vaccinated with a gB vaccine but who had later been infected with CMV. The ELISA was linear over a wide range of CMV concentrations (57-16,814 ELISA units/mL) and was reproducible as indicated by a 5% intra-day and 7% inter-day coefficients of variation. The signal was specifically competed by UL32/pp150 [862-1048] peptide but not by CMV-gB or herpes simplex virus 2 glycoprotein D. Lipid and hemoglobin matrix did not interfere with the assay. The UL32/pp150 [862-1048] IgG ELISA can be used for the sensitive and specific detection of CMV infection in gB-vaccinated individuals. Copyright © 2017 Elsevier B.V. All rights reserved.

The Effects of Varying Ratios of Physical and Mental Practice, and Task Difficulty on Performance of a Tonal Pattern

ERIC Educational Resources Information Center

Cahn, Dan

2008-01-01

Sixty undergraduate students who had completed at least one semester of jazz improvisation were assigned to either: (a) physical practice (PP); (b) mental practice (MP); (c) combined 66 percent PP and 33 percent MP (66%PP:33%MP); and (d) combined 33 percent PP and 66 percent MP (33%PP:66%MP) groups. Subjects were to perform a 3-1-7-5 tonal pattern…

Molecular characterization of a phloem-specific gene encoding the filament protein, phloem protein 1 (PP1), from Cucurbita maxima.

PubMed

Clark, A M; Jacobsen, K R; Bostwick, D E; Dannenhoffer, J M; Skaggs, M I; Thompson, G A

1997-07-01

Sieve elements in the phloem of most angiosperms contain proteinaceous filaments and aggregates called P-protein. In the genus Cucurbita, these filaments are composed of two major proteins: PP1, the phloem filament protein, and PP2, the phloem lactin. The gene encoding the phloem filament protein in pumpkin (Cucurbita maxima Duch.) has been isolated and characterized. Nucleotide sequence analysis of the reconstructed gene gPP1 revealed a continuous 2430 bp protein coding sequence, with no introns, encoding an 809 amino acid polypeptide. The deduced polypeptide had characteristics of PP1 and contained a 15 amino acid sequence determined by N-terminal peptide sequence analysis of PP1. The sequence of PP1 was highly repetitive with four 200 amino acid sequence domains containing structural motifs in common with cysteine proteinase inhibitors. Expression of the PP1 gene was detected in roots, hypocotyls, cotyledons, stems, and leaves of pumpkin plants. PP1 and its mRNA accumulated in pumpkin hypocotyls during the period of rapid hypocotyl elongation after which mRNA levels declined, while protein levels remained elevated. PP1 was immunolocalized in slime plugs and P-protein bodies in sieve elements of the phloem. Occasionally, PP1 was detected in companion cells. PP1 mRNA was localized by in situ hybridization in companion cells at early stages of vascular differentiation. The developmental accumulation and localization of PP1 and its mRNA paralleled the phloem lactin, further suggesting an interaction between these phloem-specific proteins.

Protein Phosphatase 2A Regulates Innate Immune and Proteolytic Responses to Cigarette Smoke Exposure in the Lung

PubMed Central

Wallace, Alison M.; Hardigan, Andrew; Geraghty, Patrick; Salim, Shaneeza; Gaffney, Adam; Thankachen, Jincy; Arellanos, Leo; D'Armiento, Jeanine M.; Foronjy, Robert F.

2012-01-01

Protein phosphatase 2A (PP2A) is the primary serine-threonine phosphatase of eukaryotic cells, and changes in its activity have been linked to neoplastic and neurodegenerative diseases. However, the role of PP2A in noncancerous lung diseases such as chronic obstructive pulmonary disease (COPD) has not been previously examined. This study determined that PP2A activity was significantly increased in the lungs of advanced emphysema subjects compared with age-matched controls. Furthermore, we found that cigarette smoke exposure increases PP2A activity in mouse lung in vivo and in primary human small airway epithelial (SAE) cells in vitro. In mice, intratracheal transfection of PP2A protein prior to cigarette smoke exposure prevented acute smoke–induced lung inflammation. Conversely, inhibiting PP2A activity during smoke exposure exacerbated inflammatory responses in the lung. To further determine how PP2A modulates the responses to cigarette smoke in the lung, enzyme levels were manipulated in SAE cells using protein transfection and short hairpin RNA (shRNA) techniques. Increasing PP2A activity in SAE cells via PP2A protein transfection downregulated cytokine expression and prevented the induction of proteases following cigarette smoke extract (CSE) treatment. Conversely, decreasing enzymatic activity by stably transfecting SAE cells with shRNA for the A subunit of PP2A exacerbated these smoke-mediated responses. This study establishes that PP2A induction by cigarette smoke modulates immune and proteolytic responses to cigarette smoke exposure. Together, these findings suggest that manipulation of PP2A activity may be a plausible means to treat COPD and other inflammatory diseases. PMID:22223484

Differential partitioning and speciation of Hg in wet FGD facilities of two Spanish PCC power plants.

PubMed

Ochoa-González, R; Córdoba, P; Díaz-Somoano, M; Font, O; López-Antón, M A; Leiva, C; Martínez-Tarazona, M R; Querol, X; Pereira, C Fernández; Tomás, A; Gómez, P; Mesado, P

2011-10-01

This paper evaluates the speciation and partitioning of mercury in two Spanish pulverised coal combustion power plants (PP1 and PP2), equipped with wet limestone-based flue gas desulphurisation facilities (FGD) operating with forced oxidation and re-circulation of FGD water streams. These plants are fed with coal (PP1) and coal/pet-coke blends (PP2) with different mercury contents. The behaviour, partitioning and speciation of Hg were found to be similar during the combustion processes but different in the FGD systems of the two power plants. A high proportion (86-88%) of Hg escaped the electrostatic precipitator in gaseous form, Hg2+ being the predominant mercury species (68-86%) to enter the FGD. At this point, a relatively high total Hg retention (72% and 65%) was achieved in the PP1 and PP2 (2007) FGD facilities respectively. However, during the second sampling campaign for PP2 (2008), the mercury removal achieved by the FGD was much lower (26%). Lab-scale tests point to liquid/gas ratio as the main parameter affecting oxidised mercury capture in the scrubber. The partitioning of the gaseous mercury reaching the FGD system in the wastes and by-products differed. In the low mercury input power plant (PP1) most of the mercury (67%) was associated with the FGD gypsum. Moreover in PP2 a significant proportion of the gaseous mercury reaching the FGD system remained in the aqueous phase (45%) in the 2007 sampling campaign while most of it escaped in 2008 (74%). This may be attributed to the scrubber operating conditions and the different composition and chemistry of the scrubber solution probably due to the use of an additive. Copyright © 2011 Elsevier Ltd. All rights reserved.

Diagrammatic approach to meson production in proton-proton collisions near threshold

NASA Astrophysics Data System (ADS)

Kaiser, Norbert

2000-06-01

We evaluate the threshold T-matrices for the reactions pp→ppπ0, pnπ+, ppη, ppω, pΛK+ and pn→pnη in a relativistic Feynman diagram approach. We employ an effective range approximation to take care of the strong S-wave pN and pΛ final state interaction. We stress that the heavy baryon formalism is not applicable in the NN-system above π-production threshold due to the large external momentum, |p⃗|≃√Mmπ . The magnitudes of the experimental threshold amplitudes extracted from total cross section data, A=(2.7-0.3i) fm4, B=(2.8-1.5i) fm4, |C|=1.32 fm4, |Ω|=0.53 fm4, K=√2|Ks|2+|Kt|2 =0.38 fm4 and |D|=2.3 fm4 can be reproduced by (long-range) one-pion exchange and short-range vector meson exchanges, with the latter giving the largest contributions. Pion loop effects in pp→ppπ0 appear to be small. The presented diagrammatic approach requires further tests via studies of angular distributions and polarization observables.

Role of PP2Cα in cell growth, in radio- and chemosensitivity, and in tumorigenicity

PubMed Central

Lammers, Twan; Peschke, Peter; Ehemann, Volker; Debus, Jürgen; Slobodin, Boris; Lavi, Sara; Huber, Peter

2007-01-01

Background PP2Cα is the representative member of the type 2C family of protein phosphatases, and it has recently been implicated in the regulation of p53-, TGFβ-, cyclin-dependent kinase- and apoptosis-signaling. To investigate the role of PP2Cα in cell growth and in radio- and chemosensitivity, wild type and PP2Cα siRNA-expressing MCF7 cells were subjected to several different viability and cell cycle analyses, both under basal conditions and upon treatment with radio- and chemotherapy. By comparing the growth of tumors established from both types of cells, we also evaluated the involvement of PP2Cα in tumorigenesis. Results It was found that knockdown of PP2Cα did not affect the proliferation, the clonogenic survival and the membrane integrity of MCF7 cells. In addition, it did not alter their radio- and chemosensitivity. For PP2Cα siRNA-expressing MCF7 cells, the number of cells in the G0/G1 phase of the cell cycle was reduced, the induction of the G1 block was attenuated, the number of cells in G2/M was increased, and the induction of the G2 block was enhanced. The tumorigenic potential of PP2Cα siRNA-expressing MCF7 cells was found to be higher than that of wild type MCF7 cells, and the in vivo proliferation of these cells was found to be increased. Conclusion Based on these findings, we conclude that PP2Cα is not involved in controlling cell growth and radio- and chemosensitivity in vitro. It does, however, play a role in the regulation of the cell cycle, in the induction of cell cycle checkpoints and in tumorigenesis. The latter notion implies that PP2Cα may possess tumor-suppressing properties, and it thereby sets the stage for more elaborate analyses on its involvement in the development and progression of cancer. PMID:17941990

Effect of pancreatic polypeptide on gallbladder pressure and hepatic bile secretion.

PubMed

Adrian, T E; Mitchenere, P; Sagor, G; Bloom, S R

1982-09-01

Intraluminal gallbladder pressure, measured by radiotelemetry, and bile output were monitored during infusion of porcine pancreatic polypeptide (PP) at doses of 6, 25, 100, and 400 pmol . kg-1 . h-1 in healthy conscious pigs. Plasma PP concentrations during infusion of the three lower doses, measured by radioimmunoassay, were within the range seen postprandially in these animals. Gallbladder pressure fell in a dose-related manner during PP infusion by 2.2 +/- 0.9, 8.2 +/- 0.4, 11.6 +/- 0.7, and 14.8 +/- 0.8 mmHg, respectively. In addition, a significant reduction in the bile output was observed during infusion of the two higher doses of PP. In a separate series of experiments, using cholecystectomized pigs, PP had no effect on bile output. These findings suggest that the amount of PP released postprandially may be sufficient to influence gallbladder function but not hepatic secretion of bile in the pig.

Dormancy-Associated MADS-Box (DAM) and the Abscisic Acid Pathway Regulate Pear Endodormancy Through a Feedback Mechanism.

PubMed

Tuan, Pham Anh; Bai, Songling; Saito, Takanori; Ito, Akiko; Moriguchi, Takaya

2017-08-01

In the pear 'Kosui' (Pyrus pyrifolia Nakai), the dormancy-associated MADS-box (PpDAM1 = PpMADS13-1) gene has been reported to play an essential role in bud endodormancy. Here, we found that PpDAM1 up-regulated expression of 9-cis-epoxycarotenoid dioxygenase (PpNCED3), which is a rate-limiting gene for ABA biosynthesis. Transient assays with a dual luciferase reporter system (LUC assay) and electrophoretic mobility shift assay (EMSA) showed that PpDAM1 activated PpNCED3 expression by binding to the CArG motif in the PpNCED3 promoter. PpNCED3 expression was increased toward endodormancy release in lateral flower buds of 'Kosui', which is consistent with the induced levels of ABA, its catabolism (ABA 8'-hydroxylase) and signaling genes (type 2C protein phosphatase genes and SNF1-related protein kinase 2 genes). In addition, we found that an ABA response element (ABRE)-binding transcription factor, PpAREB1, exhibiting high expression concomitant with endodormancy release, bound to three ABRE motifs in the promoter region of PpDAM1 and negatively regulated its activity. Taken together, our results suggested a feedback regulation between PpDAM1 and the ABA metabolism and signaling pathway during endodormancy of pear. This first evidence of an interaction between a DAM and ABA biosynthesis in vitro will provide further insights into bud endodormancy regulatory mechanisms of deciduous trees including pear. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Accuracy of enhanced and unenhanced MRI in diagnosing scaphoid proximal pole avascular necrosis and predicting surgical outcome.

PubMed

Fox, M G; Wang, D T; Chhabra, A B

2015-11-01

Determine the sensitivity, specificity and accuracy of unenhanced and enhanced MRI in diagnosing scaphoid proximal pole (PP) avascular necrosis (AVN) and correlate whether MRI can help guide the selection of a vascularized or nonvascularized bone graft. The study was approved by the IRB. Two MSK radiologists independently performed a retrospective review of unenhanced and enhanced MRIs from 18 patients (16 males, 2 females; median age, 17.5 years) with scaphoid nonunions and surgery performed within 65 days of the MRI. AVN was diagnosed on the unenhanced MRI when a diffusely decreased T1-W signal was present in the PP and on the enhanced MRI when PP enhancement was less than distal pole enhancement. Surgical absence of PP bleeding was diagnostic of PP AVN. Postoperative osseous union (OU) was assessed with computed tomography and/or radiographs. Sensitivity, specificity and accuracy for PP AVN were 71, 82 and 78% for unenhanced and 43, 82 and 67% for enhanced MRI. Patients with PP AVN on unenhanced MRI had 86% (6/7) OU; 100% (5/5) OU with vascularized bone grafts and 50% (1/2) OU with nonvascularized grafts. Patients with PP AVN on enhanced MRI had 80% (4/5) OU; 100% (3/3) OU with vascularized bone grafts and 50% (1/2) OU with nonvascularized grafts. Patients with viable PP on unenhanced and enhanced MRI had 91% (10/11) and 92% (12/13) OU, respectively, all but one with nonvascularized graft. When PP AVN is evident on MRI, OU is best achieved with vascularized grafts. If PP AVN is absent, OU is successful with nonvascularized grafts.

Interactions between bacterial carbon monoxide and hydrogen consumption and plant development on recent volcanic deposits.

PubMed

King, Gary M; Weber, Carolyn F

2008-02-01

Patterns of microbial colonization and interactions between microbial processes and vascular plants on volcanic deposits have received little attention. Previous reports have shown that atmospheric CO and hydrogen contribute significantly to microbial metabolism on Kilauea volcano (Hawaii) deposits with varied ages and successional development. Relationships between CO oxidation and plant communities were not clear, however, since deposit age and vegetation status covaried. To determine plant-microbe interactions in deposits of uniform ages, CO and hydrogen dynamics have been assayed for unvegetated tephra on a 1959 deposit at Pu'u Puai (PP-bare), at the edge of tree 'islands' within the PP deposit (PP-edge) and within PP tree islands (PP-canopy). Similar assays have been conducted for vegetated and unvegetated sites on a 1969 Mauna Ulu (MU) lava flow. Net in situ atmospheric CO uptake was highest at PP-edge and PP-bare sites (2.2+/-0.5 and 1.3+/-0.1 mg CO m(-2) day(-1), respectively), and least for PP-canopy (-3.2+/-0.9 mg CO m(-2) day(-1), net emission). Respiration rates, microbial biomass and maximum CO uptake potential showed an opposing pattern. Comparisons of atmospheric CO uptake and CO(2) production rates indicate that CO contributes significantly to microbial metabolism in PP-bare and MU-unvegetated sites, but negligibly where vegetation is well developed. Nonetheless, maximum potential CO uptake rates indicate that CO oxidizer populations increase with increasing plant biomass and consume CO actively. Some of these CO oxidizers may contribute to elevated nitrogen fixation rates (acetylene reduction) measured within tree islands, and thus, support plant successional development.

Measurement of the inclusive W and Z production cross sections in pp collisions at $$ \\sqrt {s} = 7 $$ TeV with the CMS experiment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chatrchyan, Serguei; et al.

2011-10-01

A measurement of inclusive W and Z production cross sections in pp collisions at sqrt(s)=7 TeV is presented. The electron and muon decay channels are analyzed in a data sample collected with the CMS detector at the LHC and corresponding to an integrated luminosity of 36 inverse picobarns. The measured inclusive cross sections are sigma(pp-> WX) B(W-> l nu) = 10.30 +/- 0.02 (stat.) +/- 0.10 (syst.) +/- 0.10 (th.) +/- 0.41 (lumi.) nb and sigma(pp -> ZX) B(Z-> l^+l^-) = 0.974 +/- 0.007 (stat.) +/- 0.007 (syst.) +/- 0.018 (th.) +/- 0.039 (lumi.) nb, limited to the dilepton invariantmore » mass range 60 to 120 GeV. The luminosity-independent cross section ratios are [sigma(pp->WX) B(W-> l nu)]/[sigma(pp-> ZX) B(Z->l^+l^-)] = 10.54 +/- 0.07 (stat.) +/- 0.08 (syst.) +/- 0.16 (th.) and [sigma(pp->W^+X) B(W^+ -> l^+nu)] / [sigma(pp->W^- X) B(W^- -> l^- nu)] = 1.421 +/- 0.006 (stat.) +/- 0.014 (syst.) +/- 0.029 (th.). The measured values agree with next-to-next-to-leading order QCD cross section calculations based on recent parton distribution functions.« less

Characterising primary productivity measurements across a dynamic western boundary current region

NASA Astrophysics Data System (ADS)

Everett, Jason D.; Doblin, Martina A.

2015-06-01

Determining the magnitude of primary production (PP) in a changing ocean is a major research challenge. Thousands of estimates of marine PP exist globally, but there remain significant gaps in data availability, particularly in the Southern Hemisphere. In situ PP estimates are generally single-point measurements and therefore we rely on satellite models of PP in order to scale up over time and space. To reduce the uncertainty around the model output, these models need to be assessed against in situ measurements before use. This study examined the vertically-integrated productivity in four water-masses associated with the East Australian Current (EAC), the major western boundary current (WBC) of the South Pacific. We calculated vertically integrated PP from shipboard 14C PP estimates and then compared them to estimates from four commonly used satellite models (ESQRT, VGPM, VGPM-Eppley, VGPM-Kameda) to assess their utility for this region. Vertical profiles of the water-column show each water-mass had distinct temperature-salinity signatures. The depth of the fluorescence-maximum (fmax) increased from onshore (river plume) to offshore (EAC) as light penetration increased. Depth integrated PP was highest in river plumes (792±181 mg C m-2 d-1) followed by the EAC (534±116 mg C m-2 d-1), continental shelf (140±47 mg C m-2 d-1) and cyclonic eddy waters (121±4 mg C m-2 d-1). Surface carbon assimilation efficiency was greatest in the EAC (301±145 mg C (mg Chl-a)-1 d-1) compared to other water masses. All satellite primary production models tested underestimated EAC PP and overestimated continental shelf PP. The ESQRT model had the highest skill and lowest bias of the tested models, providing the best first-order estimates of PP on the continental shelf, including at a coastal time-series station, Port Hacking, which showed considerable inter-annual variability (155-2957 mg C m-2 d-1). This work provides the first estimates of depth integrated PP associated with the East Australian Current in temperate Australia. The ongoing intensification of all WBCs makes it critical to understand the variability in PP at the regional scale. More accurate predictions in the EAC region will require vertically-resolved in situ productivity and bio-optical measurements across multiple time scales to allow development of other models which simulate dynamic ocean conditions.

Group A PP2Cs evolved in land plants as key regulators of intrinsic desiccation tolerance

PubMed Central

Komatsu, Kenji; Suzuki, Norihiro; Kuwamura, Mayuri; Nishikawa, Yuri; Nakatani, Mao; Ohtawa, Hitomi; Takezawa, Daisuke; Seki, Motoaki; Tanaka, Maho; Taji, Teruaki; Hayashi, Takahisa; Sakata, Yoichi

2013-01-01

Vegetative desiccation tolerance is common in bryophytes, although this character has been lost in most vascular plants. The moss Physcomitrella patens survives complete desiccation if treated with abscisic acid (ABA). Group A protein phosphatases type 2C (PP2C) are negative regulators of abscisic acid signalling. Here we show that the elimination of Group A PP2C is sufficient to ensure P. patens survival to full desiccation, without ABA treatment, although its growth is severely hindered. Microarray analysis shows that the Group A PP2C-regulated genes exclusively overlap with genes exhibiting a high level of ABA induction. Group A PP2C disruption weakly affects ABA-activated kinase activity, indicating Group A PP2C action downstream of these kinases in the moss. We propose that Group A PP2C emerged in land plants to repress desiccation tolerance mechanisms, possibly facilitating plants propagation on land, whereas ABA releases the intrinsic desiccation tolerance from Group A PP2C regulation. PMID:23900426

Search for Bs0 --> micro+ micro- and B0 --> micro+ micro- decays with 2 fb-1 of pp collisions.

PubMed

Aaltonen, T; Adelman, J; Akimoto, T; Albrow, M G; Alvarez González, B; Amerio, S; Amidei, D; Anastassov, A; Annovi, A; Antos, J; Aoki, M; Apollinari, G; Apresyan, A; Arisawa, T; Artikov, A; Ashmanskas, W; Attal, A; Aurisano, A; Azfar, F; Azzi-Bacchetta, P; Azzurri, P; Bacchetta, N; Badgett, W; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Baroiant, S; Bartsch, V; Bauer, G; Beauchemin, P-H; Bedeschi, F; Bednar, P; Behari, S; Bellettini, G; Bellinger, J; Belloni, A; Benjamin, D; Beretvas, A; Beringer, J; Berry, T; Bhatti, A; Binkley, M; Bisello, D; Bizjak, I; Blair, R E; Blocker, C; Blumenfeld, B; Bocci, A; Bodek, A; Boisvert, V; Bolla, G; Bolshov, A; Bortoletto, D; Boudreau, J; Boveia, A; Brau, B; Bridgeman, A; Brigliadori, L; Bromberg, C; Brubaker, E; Budagov, J; Budd, H S; Budd, S; Burkett, K; Busetto, G; Bussey, P; Buzatu, A; Byrum, K L; Cabrera, S; Campanelli, M; Campbell, M; Canelli, F; Canepa, A; Carlsmith, D; Carosi, R; Carrillo, S; Carron, S; Casal, B; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chang, S H; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, K; Chokheli, D; Chou, J P; Choudalakis, G; Chuang, S H; Chung, K; Chung, W H; Chung, Y S; Ciobanu, C I; Ciocci, M A; Clark, A; Clark, D; Compostella, G; Convery, M E; Conway, J; Cooper, B; Copic, K; Cordelli, M; Cortiana, G; Crescioli, F; Cuenca Almenar, C; Cuevas, J; Culbertson, R; Cully, J C; Dagenhart, D; Datta, M; Davies, T; de Barbaro, P; De Cecco, S; Deisher, A; De Lentdecker, G; De Lorenzo, G; Dell'orso, M; Demortier, L; Deng, J; Deninno, M; De Pedis, D; Derwent, P F; Di Giovanni, G P; Dionisi, C; Di Ruzza, B; Dittmann, J R; D'Onofrio, M; Donati, S; Dong, P; Donini, J; Dorigo, T; Dube, S; Efron, J; Erbacher, R; Errede, D; Errede, S; Eusebi, R; Fang, H C; Farrington, S; Fedorko, W T; Feild, R G; Feindt, M; Fernandez, J P; Ferrazza, C; Field, R; Flanagan, G; Forrest, R; Forrester, S; Franklin, M; Freeman, J C; Furic, I; Gallinaro, M; Galyardt, J; Garberson, F; Garcia, J E; Garfinkel, A F; Genser, K; Gerberich, H; Gerdes, D; Giagu, S; Giakoumopolou, V; Giannetti, P; Gibson, K; Gimmell, J L; Ginsburg, C M; Giokaris, N; Giordani, M; Giromini, P; Giunta, M; Glagolev, V; Glenzinski, D; Gold, M; Goldschmidt, N; Golossanov, A; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gresele, A; Grinstein, S; Grosso-Pilcher, C; Grundler, U; Guimaraes da Costa, J; Gunay-Unalan, Z; Haber, C; Hahn, K; Hahn, S R; Halkiadakis, E; Hamilton, A; Han, B-Y; Han, J Y; Handler, R; Happacher, F; Hara, K; Hare, D; Hare, M; Harper, S; Harr, R F; Harris, R M; Hartz, M; Hatakeyama, K; Hauser, J; Hays, C; Heck, M; Heijboer, A; Heinemann, B; Heinrich, J; Henderson, C; Herndon, M; Heuser, J; Hewamanage, S; Hidas, D; Hill, C S; Hirschbuehl, D; Hocker, A; Hou, S; Houlden, M; Hsu, S-C; Huffman, B T; Hughes, R E; Husemann, U; Huston, J; Incandela, J; Introzzi, G; Iori, M; Ivanov, A; Iyutin, B; James, E; Jayatilaka, B; Jeans, D; Jeon, E J; Jindariani, S; Johnson, W; Jones, M; Joo, K K; Jun, S Y; Jung, J E; Junk, T R; Kamon, T; Kar, D; Karchin, P E; Kato, Y; Kephart, R; Kerzel, U; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kimura, N; Kirsch, L; Klimenko, S; Klute, M; Knuteson, B; Ko, B R; Koay, S A; Kondo, K; Kong, D J; Konigsberg, J; Korytov, A; Kotwal, A V; Kraus, J; Kreps, M; Kroll, J; Krumnack, N; Kruse, M; Krutelyov, V; Kubo, T; Kuhlmann, S E; Kuhr, T; Kulkarni, N P; Kusakabe, Y; Kwang, S; Laasanen, A T; Lai, S; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; Lazzizzera, I; Lecompte, T; Lee, J; Lee, J; Lee, Y J; Lee, S W; Lefèvre, R; Leonardo, N; Leone, S; Levy, S; Lewis, J D; Lin, C; Lin, C S; Linacre, J; Lindgren, M; Lipeles, E; Lister, A; Litvintsev, D O; Liu, T; Lockyer, N S; Loginov, A; Loreti, M; Lovas, L; Lu, R-S; Lucchesi, D; Lueck, J; Luci, C; Lujan, P; Lukens, P; Lungu, G; Lyons, L; Lys, J; Lysak, R; Lytken, E; Mack, P; Macqueen, D; Madrak, R; Maeshima, K; Makhoul, K; Maki, T; Maksimovic, P; Malde, S; Malik, S; Manca, G; Manousakis, A; Margaroli, F; Marino, C; Marino, C P; Martin, A; Martin, M; Martin, V; Martínez, M; Martínez-Ballarín, R; Maruyama, T; Mastrandrea, P; Masubuchi, T; Mattson, M E; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Menzemer, S; Menzione, A; Merkel, P; Mesropian, C; Messina, A; Miao, T; Miladinovic, N; Miles, J; Miller, R; Mills, C; Milnik, M; Mitra, A; Mitselmakher, G; Miyake, H; Moed, S; Moggi, N; Moon, C S; Moore, R; Morello, M; Movilla Fernandez, P; Mülmenstädt, J; Mukherjee, A; Muller, Th; Mumford, R; Murat, P; Mussini, M; Nachtman, J; Nagai, Y; Nagano, A; Naganoma, J; Nakamura, K; Nakano, I; Napier, A; Necula, V; Neu, C; Neubauer, M S; Nielsen, J; Nodulman, L; Norman, M; Norniella, O; Nurse, E; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Oldeman, R; Orava, R; Osterberg, K; Pagan Griso, S; Pagliarone, C; Palencia, E; Papadimitriou, V; Papaikonomou, A; Paramonov, A A; Parks, B; Pashapour, S; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Piedra, J; Pinera, L; Pitts, K; Plager, C; Pondrom, L; Portell, X; Poukhov, O; Pounder, N; Prakoshyn, F; Pronko, A; Proudfoot, J; Ptohos, F; Punzi, G; Pursley, J; Rademacker, J; Rahaman, A; Ramakrishnan, V; Ranjan, N; Redondo, I; Reisert, B; Rekovic, V; Renton, P; Rescigno, M; Richter, S; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rogers, E; Rolli, S; Roser, R; Rossi, M; Rossin, R; Roy, P; Ruiz, A; Russ, J; Rusu, V; Saarikko, H; Safonov, A; Sakumoto, W K; Salamanna, G; Saltó, O; Santi, L; Sarkar, S; Sartori, L; Sato, K; Savoy-Navarro, A; Scheidle, T; Schlabach, P; Schmidt, E E; Schmidt, M A; Schmidt, M P; Schmitt, M; Schwarz, T; Scodellaro, L; Scott, A L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semenov, A; Sexton-Kennedy, L; Sfyria, A; Shalhout, S Z; Shapiro, M D; Shears, T; Shepard, P F; Sherman, D; Shimojima, M; Shochet, M; Shon, Y; Shreyber, I; Sidoti, A; Sinervo, P; Sisakyan, A; Slaughter, A J; Slaunwhite, J; Sliwa, K; Smith, J R; Snider, F D; Snihur, R; Soderberg, M; Soha, A; Somalwar, S; Sorin, V; Spalding, J; Spinella, F; Spreitzer, T; Squillacioti, P; Stanitzki, M; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Stuart, D; Suh, J S; Sukhanov, A; Sun, H; Suslov, I; Suzuki, T; Taffard, A; Takashima, R; Takeuchi, Y; Tanaka, R; Tecchio, M; Teng, P K; Terashi, K; Thom, J; Thompson, A S; Thompson, G A; Thomson, E; Tipton, P; Tiwari, V; Tkaczyk, S; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Tourneur, S; Trischuk, W; Tu, Y; Turini, N; Ukegawa, F; Uozumi, S; Vallecorsa, S; van Remortel, N; Varganov, A; Vataga, E; Vázquez, F; Velev, G; Vellidis, C; Veszpremi, V; Vidal, M; Vidal, R; Vila, I; Vilar, R; Vine, T; Vogel, M; Volobouev, I; Volpi, G; Würthwein, F; Wagner, P; Wagner, R G; Wagner, R L; Wagner-Kuhr, J; Wagner, W; Wakisaka, T; Wallny, R; Wang, S M; Warburton, A; Waters, D; Weinberger, M; Wester, W C; Whitehouse, B; Whiteson, D; Wicklund, A B; Wicklund, E; Williams, G; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, C; Wright, T; Wu, X; Wynne, S M; Yagil, A; Yamamoto, K; Yamaoka, J; Yamashita, T; Yang, C; Yang, U K; Yang, Y C; Yao, W M; Yeh, G P; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanello, L; Zanetti, A; Zaw, I; Zhang, X; Zheng, Y; Zucchelli, S

2008-03-14

We have performed a search for B(s)(0) --> micro(+) micro(-) and B(0) --> micro(+) micro(-) decays in pp collisions at square root s = 1.96 TeV using 2 fb(-1) of integrated luminosity collected by the CDF II detector at the Fermilab Tevatron Collider. The observed number of B(s)(0) and B0 candidates is consistent with background expectations. The resulting upper limits on the branching fractions are B(B(s)0) --> micro(+) micro(-)) <5.8 x 10(-8) and B(B(0) --> micro(+) micro(-))<1.8 x 10(-8) at 95% C.L.

PP2A-activating drugs selectively eradicate TKI-resistant chronic myeloid leukemic stem cells

PubMed Central

Neviani, Paolo; Harb, Jason G.; Oaks, Joshua J.; Santhanam, Ramasamy; Walker, Christopher J.; Ellis, Justin J.; Ferenchak, Gregory; Dorrance, Adrienne M.; Paisie, Carolyn A.; Eiring, Anna M.; Ma, Yihui; Mao, Hsiaoyin C.; Zhang, Bin; Wunderlich, Mark; May, Philippa C.; Sun, Chaode; Saddoughi, Sahar A.; Bielawski, Jacek; Blum, William; Klisovic, Rebecca B.; Solt, Janelle A.; Byrd, John C.; Volinia, Stefano; Cortes, Jorge; Huettner, Claudia S.; Koschmieder, Steffen; Holyoake, Tessa L.; Devine, Steven; Caligiuri, Michael A.; Croce, Carlo M.; Garzon, Ramiro; Ogretmen, Besim; Arlinghaus, Ralph B.; Chen, Ching-Shih; Bittman, Robert; Hokland, Peter; Roy, Denis-Claude; Milojkovic, Dragana; Apperley, Jane; Goldman, John M.; Reid, Alistair; Mulloy, James C.; Bhatia, Ravi; Marcucci, Guido; Perrotti, Danilo

2013-01-01

The success of tyrosine kinase inhibitors (TKIs) in treating chronic myeloid leukemia (CML) depends on the requirement for BCR-ABL1 kinase activity in CML progenitors. However, CML quiescent HSCs are TKI resistant and represent a BCR-ABL1 kinase–independent disease reservoir. Here we have shown that persistence of leukemic HSCs in BM requires inhibition of the tumor suppressor protein phosphatase 2A (PP2A) and expression — but not activity — of the BCR-ABL1 oncogene. Examination of HSCs from CML patients and healthy individuals revealed that PP2A activity was suppressed in CML compared with normal HSCs. TKI-resistant CML quiescent HSCs showed increased levels of BCR-ABL1, but very low kinase activity. BCR-ABL1 expression, but not kinase function, was required for recruitment of JAK2, activation of a JAK2/β-catenin survival/self-renewal pathway, and inhibition of PP2A. PP2A-activating drugs (PADs) markedly reduced survival and self-renewal of CML quiescent HSCs, but not normal quiescent HSCs, through BCR-ABL1 kinase–independent and PP2A-mediated inhibition of JAK2 and β-catenin. This led to suppression of human leukemic, but not normal, HSC/progenitor survival in BM xenografts and interference with long-term maintenance of BCR-ABL1–positive HSCs in serial transplantation assays. Targeting the JAK2/PP2A/β-catenin network in quiescent HSCs with PADs (e.g., FTY720) has the potential to treat TKI-refractory CML and relieve lifelong patient dependence on TKIs. PMID:23999433

Bovine pancreatic polypeptide (bPP) undergoes significant changes in conformation and dynamics upon binding to DPC micelles.

PubMed

Lerch, Mirjam; Gafner, Verena; Bader, Reto; Christen, Barbara; Folkers, Gerd; Zerbe, Oliver

2002-10-04

The pancreatic polypeptide (PP), a 36-residue, C-terminally amidated polypeptide hormone is a member of the neuropeptide Y (NPY) family. Here, we have studied the structure and dynamics of bovine pancreatic polypeptide (bPP) when bound to DPC-micelles as a membrane-mimicking model as well as the dynamics of bPP in solution. The comparison of structure and dynamics of bPP in both states reveals remarkable differences. The overall correlation time of 5.08ns derived from the 15N relaxation data proves unambiguously that bPP in solution exists as a dimer. Therein, intermolecular as well as intramolecular hydrophobic interactions from residues of both the amphiphilic helix and of the back-folded N terminus contribute to the stability of the PP fold. The overall rigidity is well-reflected in positive values for the heteronuclear NOE for residues 4-34. The membrane-bound species displays a partitioning into a more flexible N-terminal region and a well-defined alpha-helical region comprising residues 17-31. The average RMSD value for residues 17-31 is 0.22(+/-0.09)A. The flexibility of the N terminus is compatible with negative values of the heteronuclear NOE observed for the N-terminal residues 4-12 and low values of the generalized order parameter S(2). The membrane-peptide interface was investigated by micelle-integrating spin-labels and H,2H exchange measurements. It is formed by those residues which make contacts between the C-terminal alpha-helix and the polyproline helix. In contrast to pNPY, also residues from the N terminus display spatial proximity to the membrane interface. Furthermore, the orientation of the C terminus, that presumably contains residues involved in receptor binding, is different in the two environments. We speculate that this pre-positioning of residues could be an important requirement for receptor activation. Moreover, we doubt that the PP fold is of functional relevance for binding at the Y(4) receptor.

Protease activation during in vivo pancreatitis is dependent on calcineurin activation.

PubMed

Shah, Ahsan U; Sarwar, Amna; Orabi, Abrahim I; Gautam, Samir; Grant, Wayne M; Park, Alexander J; Shah, Adnan U; Liu, Jun; Mistry, Pramod K; Jain, Dhanpat; Husain, Sohail Z

2009-11-01

The premature activation of digestive proenzymes, specifically proteases, within the pancreatic acinar cell is an early and critical event during acute pancreatitis. Our previous studies demonstrate that this activation requires a distinct pathological rise in cytosolic Ca(2+). Furthermore, we have shown that a target of aberrant Ca(2+) in acinar cells is the Ca(2+)/calmodulin-dependent phosphatase calcineurin (PP2B). In this study, we hypothesized that PP2B mediates in vivo protease activation and pancreatitis severity. To test this, pancreatitis was induced in mice over 8 h by administering hourly intraperitoneal injections of the cholecystokinin analog caerulein (50 microg/kg). Treatment with the PP2B inhibitor FK506 at 1 and 8 h after pancreatitis induction reduced trypsin activities by greater than 50% (P < 0.005). Serum amylase and IL-6 was reduced by 86 and 84% relative to baseline (P < 0.0005) at 8 h, respectively. Histological severity of pancreatitis, graded on the basis of pancreatic edema, acinar cell vacuolization, inflammation, and apoptosis, was reduced early in the course of pancreatitis. Myeloperoxidase activity from both pancreas and lung was reduced by 93 and 83% relative to baseline, respectively (P < 0.05). These data suggest that PP2B is an important target of the aberrant acinar cell Ca(2+) rise associated with pathological protease activation and pancreatitis.

Molecular mimicry regulates ABA signaling by SnRK2 kinases and PP2C phosphatases.

PubMed

Soon, Fen-Fen; Ng, Ley-Moy; Zhou, X Edward; West, Graham M; Kovach, Amanda; Tan, M H Eileen; Suino-Powell, Kelly M; He, Yuanzheng; Xu, Yong; Chalmers, Michael J; Brunzelle, Joseph S; Zhang, Huiming; Yang, Huaiyu; Jiang, Hualiang; Li, Jun; Yong, Eu-Leong; Cutler, Sean; Zhu, Jian-Kang; Griffin, Patrick R; Melcher, Karsten; Xu, H Eric

2012-01-06

Abscisic acid (ABA) is an essential hormone for plants to survive environmental stresses. At the center of the ABA signaling network is a subfamily of type 2C protein phosphatases (PP2Cs), which form exclusive interactions with ABA receptors and subfamily 2 Snfl-related kinase (SnRK2s). Here, we report a SnRK2-PP2C complex structure, which reveals marked similarity in PP2C recognition by SnRK2 and ABA receptors. In the complex, the kinase activation loop docks into the active site of PP2C, while the conserved ABA-sensing tryptophan of PP2C inserts into the kinase catalytic cleft, thus mimicking receptor-PP2C interactions. These structural results provide a simple mechanism that directly couples ABA binding to SnRK2 kinase activation and highlight a new paradigm of kinase-phosphatase regulation through mutual packing of their catalytic sites.

Measurement of inclusive W and Z boson production cross sections in pp collisions at sqrt[s] = 8 TeV.

PubMed

Chatrchyan, S; Khachatryan, V; Sirunyan, A M; Tumasyan, A; Adam, W; Bergauer, T; Dragicevic, M; Erö, J; Fabjan, C; Friedl, M; Frühwirth, R; Ghete, V M; Hörmann, N; Hrubec, J; Jeitler, M; Kiesenhofer, W; Knünz, V; Krammer, M; Krätschmer, I; Liko, D; Mikulec, I; Rabady, D; Rahbaran, B; Rohringer, C; Rohringer, H; Schöfbeck, R; Strauss, J; Taurok, A; Treberer-Treberspurg, W; Waltenberger, W; Wulz, C-E; Mossolov, V; Shumeiko, N; Suarez Gonzalez, J; Alderweireldt, S; Bansal, M; Bansal, S; Cornelis, T; De Wolf, E A; Janssen, X; Knutsson, A; Luyckx, S; Mucibello, L; Ochesanu, S; Roland, B; Rougny, R; Van Haevermaet, H; Van Mechelen, P; Van Remortel, N; Van Spilbeeck, A; Blekman, F; Blyweert, S; D'Hondt, J; Kalogeropoulos, A; Keaveney, J; Maes, M; Olbrechts, A; Tavernier, S; Van Doninck, W; Van Mulders, P; Van Onsem, G P; Villella, I; Clerbaux, B; De Lentdecker, G; Favart, L; Gay, A P R; Hreus, T; Léonard, A; Marage, P E; Mohammadi, A; Perniè, L; Reis, T; Seva, T; Thomas, L; Vander Velde, C; Vanlaer, P; Wang, J; Adler, V; Beernaert, K; Benucci, L; Cimmino, A; Costantini, S; Dildick, S; Garcia, G; Klein, B; Lellouch, J; Marinov, A; Mccartin, J; Ocampo Rios, A A; Ryckbosch, D; Sigamani, M; Strobbe, N; Thyssen, F; Tytgat, M; Walsh, S; Yazgan, E; Zaganidis, N; Basegmez, S; Beluffi, C; Bruno, G; Castello, R; Caudron, A; Ceard, L; Delaere, C; du Pree, T; Favart, D; Forthomme, L; Giammanco, A; Hollar, J; Lemaitre, V; Liao, J; Militaru, O; Nuttens, C; Pagano, D; Pin, A; Piotrzkowski, K; Popov, A; Selvaggi, M; Vizan Garcia, J M; Beliy, N; Caebergs, T; Daubie, E; Hammad, G H; Alves, G A; Correa Martins Junior, M; Martins, T; Pol, M E; Souza, M H G; Aldá Júnior, W L; Carvalho, W; Chinellato, J; Custódio, A; Da Costa, E M; De Jesus Damiao, D; De Oliveira Martins, C; Fonseca De Souza, S; Malbouisson, H; Malek, M; Matos Figueiredo, D; Mundim, L; Nogima, H; Prado Da Silva, W L; Santoro, A; Soares Jorge, L; Sznajder, A; Tonelli Manganote, E J; Vilela Pereira, A; Anjos, T S; Bernardes, C A; Dias, F A; Fernandez Perez Tomei, T R; Gregores, E M; Lagana, C; Marinho, F; Mercadante, P G; Novaes, S F; Padula, Sandra S; Genchev, V; Iaydjiev, P; Piperov, S; Rodozov, M; Sultanov, G; Vutova, M; Dimitrov, A; Hadjiiska, R; Kozhuharov, V; Litov, L; Pavlov, B; Petkov, P; Bian, J G; Chen, G M; Chen, H S; Jiang, C H; Liang, D; Liang, S; Meng, X; Tao, J; Wang, J; Wang, X; Wang, Z; Xiao, H; Xu, M; Asawatangtrakuldee, C; Ban, Y; Guo, Y; Li, Q; Li, W; Liu, S; Mao, Y; Qian, S J; Wang, D; Zhang, L; Zou, W; Avila, C; Carrillo Montoya, C A; Gomez, J P; Gomez Moreno, B; Sanabria, J C; Godinovic, N; Lelas, D; Plestina, R; Polic, D; Puljak, I; Antunovic, Z; Kovac, M; Brigljevic, V; Duric, S; Kadija, K; Luetic, J; Mekterovic, D; Morovic, S; Tikvica, L; Attikis, A; Mavromanolakis, G; Mousa, J; Nicolaou, C; Ptochos, F; Razis, P A; Finger, M; Finger, M; Abdelalim, A A; Assran, Y; Ellithi Kamel, A; Mahmoud, M A; Radi, A; Kadastik, M; Müntel, M; Murumaa, M; Raidal, M; Rebane, L; Tiko, A; Eerola, P; Fedi, G; Voutilainen, M; Härkönen, J; Karimäki, V; Kinnunen, R; Kortelainen, M J; Lampén, T; Lassila-Perini, K; Lehti, S; Lindén, T; Luukka, P; Mäenpää, T; Peltola, T; Tuominen, E; Tuominiemi, J; Tuovinen, E; Wendland, L; Korpela, A; Tuuva, T; Besancon, M; Choudhury, S; Couderc, F; Dejardin, M; Denegri, D; Fabbro, B; Faure, J L; Ferri, F; Ganjour, S; Givernaud, A; Gras, P; Hamel de Monchenault, G; Jarry, P; Locci, E; Malcles, J; Millischer, L; Nayak, A; Rander, J; Rosowsky, A; Titov, M; Baffioni, S; Beaudette, F; Benhabib, L; Bianchini, L; Bluj, M; Busson, P; Charlot, C; Daci, N; Dahms, T; Dalchenko, M; Dobrzynski, L; Florent, A; Granier de Cassagnac, R; Haguenauer, M; Miné, P; Mironov, C; Naranjo, I N; Nguyen, M; Ochando, C; Paganini, P; Sabes, D; Salerno, R; Sirois, Y; Veelken, C; Zabi, A; Agram, J-L; Andrea, J; Bloch, D; Bodin, D; Brom, J-M; Chabert, E C; Collard, C; Conte, E; Drouhin, F; Fontaine, J-C; Gelé, D; Goerlach, U; Goetzmann, C; Juillot, P; Le Bihan, A-C; Van Hove, P; Gadrat, S; Beauceron, S; Beaupere, N; Boudoul, G; Brochet, S; Chasserat, J; Chierici, R; Contardo, D; Depasse, P; El Mamouni, H; Fay, J; Gascon, S; Gouzevitch, M; Ille, B; Kurca, T; Lethuillier, M; Mirabito, L; Perries, S; Sgandurra, L; Sordini, V; Tschudi, Y; Vander Donckt, M; Verdier, P; Viret, S; Tsamalaidze, Z; Autermann, C; Beranek, S; Calpas, B; Edelhoff, M; Feld, L; Heracleous, N; Hindrichs, O; Klein, K; Merz, J; Ostapchuk, A; Perieanu, A; Raupach, F; Sammet, J; Schael, S; Sprenger, D; Weber, H; Wittmer, B; Zhukov, V; Ata, M; Caudron, J; Dietz-Laursonn, E; Duchardt, D; Erdmann, M; Fischer, R; Güth, A; Hebbeker, T; Heidemann, C; Hoepfner, K; Klingebiel, D; Kreuzer, P; Merschmeyer, M; Meyer, A; Olschewski, M; Padeken, K; Papacz, P; Pieta, H; Reithler, H; Schmitz, S A; Sonnenschein, L; Steggemann, J; Teyssier, D; Thüer, S; Weber, M; Cherepanov, V; Erdogan, Y; Flügge, G; Geenen, H; Geisler, M; Haj Ahmad, W; Hoehle, F; Kargoll, B; Kress, T; Kuessel, Y; Lingemann, J; Nowack, A; Nugent, I M; Perchalla, L; Pooth, O; Stahl, A; Aldaya Martin, M; Asin, I; Bartosik, N; Behr, J; Behrenhoff, W; Behrens, U; Bergholz, M; Bethani, A; Borras, K; Burgmeier, A; Cakir, A; Calligaris, L; Campbell, A; Costanza, F; Diez Pardos, C; Dorland, T; Eckerlin, G; Eckstein, D; Flucke, G; Geiser, A; Glushkov, I; Gunnellini, P; Habib, S; Hauk, J; Hellwig, G; Jung, H; Kasemann, M; Katsas, P; Kleinwort, C; Kluge, H; Krämer, M; Krücker, D; Kuznetsova, E; Lange, W; Leonard, J; Lipka, K; Lohmann, W; Lutz, B; Mankel, R; Marfin, I; Melzer-Pellmann, I-A; Meyer, A B; Mnich, J; Mussgiller, A; Naumann-Emme, S; Novgorodova, O; Nowak, F; Olzem, J; Perrey, H; Petrukhin, A; Pitzl, D; Placakyte, R; Raspereza, A; Ribeiro Cipriano, P M; Riedl, C; Ron, E; Sahin, M Ö; Salfeld-Nebgen, J; Schmidt, R; Schoerner-Sadenius, T; Sen, N; Stein, M; Walsh, R; Wissing, C; Blobel, V; Enderle, H; Erfle, J; Gebbert, U; Görner, M; Gosselink, M; Haller, J; Heine, K; Höing, R S; Kaussen, G; Kirschenmann, H; Klanner, R; Kogler, R; Lange, J; Peiffer, T; Pietsch, N; Rathjens, D; Sander, C; Schettler, H; Schleper, P; Schlieckau, E; Schmidt, A; Schröder, M; Schum, T; Seidel, M; Sibille, J; Sola, V; Stadie, H; Steinbrück, G; Thomsen, J; Troendle, D; Vanelderen, L; Barth, C; Baus, C; Berger, J; Böser, C; Chwalek, T; De Boer, W; Descroix, A; Dierlamm, A; Feindt, M; Guthoff, M; Hackstein, C; Hartmann, F; Hauth, T; Heinrich, M; Held, H; Hoffmann, K H; Husemann, U; Katkov, I; Komaragiri, J R; Kornmayer, A; Lobelle Pardo, P; Martschei, D; Mueller, S; Müller, Th; Niegel, M; Nürnberg, A; Oberst, O; Ott, J; Quast, G; Rabbertz, K; Ratnikov, F; Röcker, S; Schilling, F-P; Schott, G; Simonis, H J; Stober, F M; Ulrich, R; Wagner-Kuhr, J; Wayand, S; Weiler, T; Zeise, M; Anagnostou, G; Daskalakis, G; Geralis, T; Kesisoglou, S; Kyriakis, A; Loukas, D; Markou, A; Markou, C; Ntomari, E; Gouskos, L; Mertzimekis, T J; Panagiotou, A; Saoulidou, N; Stiliaris, E; Aslanoglou, X; Evangelou, I; Flouris, G; Foudas, C; Kokkas, P; Manthos, N; Papadopoulos, I; Paradas, E; Bencze, G; Hajdu, C; Hidas, P; Horvath, D; Radics, B; Sikler, F; Veszpremi, V; Vesztergombi, G; Zsigmond, A J; Beni, N; Czellar, S; Molnar, J; Palinkas, J; Szillasi, Z; Karancsi, J; Raics, P; Trocsanyi, Z L; Ujvari, B; Swain, S K; Beri, S B; Bhatnagar, V; Dhingra, N; Gupta, R; Kaur, M; Mehta, M Z; Mittal, M; Nishu, N; Saini, L K; Sharma, A; Singh, J B; Kumar, Ashok; Kumar, Arun; Ahuja, S; Bhardwaj, A; Choudhary, B C; Malhotra, S; Naimuddin, M; Ranjan, K; Saxena, P; Sharma, V; Shivpuri, R K; Banerjee, S; Bhattacharya, S; Chatterjee, K; Dutta, S; Gomber, B; Jain, Sa; Jain, Sh; Khurana, R; Modak, A; Mukherjee, S; Roy, D; Sarkar, S; Sharan, M; Singh, A P; Abdulsalam, A; Dutta, D; Kailas, S; Kumar, V; Mohanty, A K; Pant, L M; Shukla, P; Topkar, A; Aziz, T; Chatterjee, R M; Ganguly, S; Ghosh, S; Guchait, M; Gurtu, A; Kole, G; Kumar, S; Maity, M; Majumder, G; Mazumdar, K; Mohanty, G B; Parida, B; Sudhakar, K; Wickramage, N; Banerjee, S; Dugad, S; Arfaei, H; Bakhshiansohi, H; Etesami, S M; Fahim, A; Hesari, H; Jafari, A; Khakzad, M; Mohammadi Najafabadi, M; Paktinat Mehdiabadi, S; Safarzadeh, B; Zeinali, M; Grunewald, M; Abbrescia, M; Barbone, L; Calabria, C; Chhibra, S S; Colaleo, A; Creanza, D; De Filippis, N; De Palma, M; Fiore, L; Iaselli, G; Maggi, G; Maggi, M; Marangelli, B; My, S; Nuzzo, S; Pacifico, N; Pompili, A; Pugliese, G; Selvaggi, G; Silvestris, L; Singh, G; Venditti, R; Verwilligen, P; Zito, G; Abbiendi, G; Benvenuti, A C; Bonacorsi, D; Braibant-Giacomelli, S; Brigliadori, L; Campanini, R; Capiluppi, P; Castro, A; Cavallo, F R; Cuffiani, M; Dallavalle, G M; Fabbri, F; Fanfani, A; Fasanella, D; Giacomelli, P; Grandi, C; Guiducci, L; Marcellini, S; Masetti, G; Meneghelli, M; Montanari, A; Navarria, F L; Odorici, F; Perrotta, A; Primavera, F; Rossi, A M; Rovelli, T; Siroli, G P; Tosi, N; Travaglini, R; Albergo, S; Chiorboli, M; Costa, S; Giordano, F; Potenza, R; Tricomi, A; Tuve, C; Barbagli, G; Ciulli, V; Civinini, C; D'Alessandro, R; Focardi, E; Frosali, S; Gallo, E; Gonzi, S; Gori, V; Lenzi, P; Meschini, M; Paoletti, S; Sguazzoni, G; Tropiano, A; Benussi, L; Bianco, S; Fabbri, F; Piccolo, D; Fabbricatore, P; Musenich, R; Tosi, S; Benaglia, A; De Guio, F; Di Matteo, L; Fiorendi, S; Gennai, S; Ghezzi, A; Govoni, P; Lucchini, M T; Malvezzi, S; Manzoni, R A; Martelli, A; Massironi, A; Menasce, D; Moroni, L; Paganoni, M; Pedrini, D; Ragazzi, S; Redaelli, N; Tabarelli de Fatis, T; Buontempo, S; Cavallo, N; De Cosa, A; Fabozzi, F; Iorio, A O M; Lista, L; Meola, S; Merola, M; Paolucci, P; Azzi, P; Bacchetta, N; Bellato, M; Bisello, D; Branca, A; Carlin, R; Checchia, P; Dorigo, T; Dosselli, U; Galanti, M; Gasparini, F; Gasparini, U; Giubilato, P; Gozzelino, A; Kanishchev, K; Lacaprara, S; Lazzizzera, I; Margoni, M; Meneguzzo, A T; Nespolo, M; Pazzini, J; Pozzobon, N; Ronchese, P; Sgaravatto, M; Simonetto, F; Torassa, E; Tosi, M; Zotto, P; Zucchetta, A; Zumerle, G; Gabusi, M; Ratti, S P; Riccardi, C; Vitulo, P; Biasini, M; Bilei, G M; Fanò, L; Lariccia, P; Mantovani, G; Menichelli, M; Nappi, A; Romeo, F; Saha, A; Santocchia, A; Spiezia, A; Androsov, K; Azzurri, P; Bagliesi, G; Bernardini, J; Boccali, T; Broccolo, G; Castaldi, R; D'Agnolo, R T; Dell'Orso, R; Fiori, F; Foà, L; Giassi, A; Kraan, A; Ligabue, F; Lomtadze, T; Martini, L; Messineo, A; Palla, F; Rizzi, A; Serban, A T; Spagnolo, P; Squillacioti, P; Tenchini, R; Tonelli, G; Venturi, A; Verdini, P G; Vernieri, C; Barone, L; Cavallari, F; Del Re, D; Diemoz, M; Fanelli, C; Grassi, M; Longo, E; Margaroli, F; Meridiani, P; Micheli, F; Nourbakhsh, S; Organtini, G; Paramatti, R; Rahatlou, S; Soffi, L; Amapane, N; Arcidiacono, R; Argiro, S; Arneodo, M; Biino, C; Cartiglia, N; Casasso, S; Costa, M; Demaria, N; Mariotti, C; Maselli, S; Mazza, G; Migliore, E; Monaco, V; Musich, M; Obertino, M M; Pastrone, N; Pelliccioni, M; Potenza, A; Romero, A; Ruspa, M; Sacchi, R; Solano, A; Staiano, A; Tamponi, U; Belforte, S; Candelise, V; Casarsa, M; Cossutti, F; Della Ricca, G; Gobbo, B; La Licata, C; Marone, M; Montanino, D; Penzo, A; Schizzi, A; Zanetti, A; Kim, T Y; Nam, S K; Chang, S; Kim, D H; Kim, G N; Kim, J E; Kong, D J; Oh, Y D; Park, H; Son, D C; Kim, J Y; Kim, Zero J; Song, S; Choi, S; Gyun, D; Hong, B; Jo, M; Kim, H; Kim, T J; Lee, K S; Park, S K; Roh, Y; Choi, M; Kim, J H; Park, C; Park, I C; Park, S; Ryu, G; Choi, Y; Choi, Y K; Goh, J; Kim, M S; Kwon, E; Lee, B; Lee, J; Lee, S; Seo, H; Yu, I; Grigelionis, I; Juodagalvis, A; Castilla-Valdez, H; De La Cruz-Burelo, E; Heredia-de La Cruz, I; Lopez-Fernandez, R; Martínez-Ortega, J; Sanchez-Hernandez, A; Villasenor-Cendejas, L M; Carrillo Moreno, S; Vazquez Valencia, F; Salazar Ibarguen, H A; Casimiro Linares, E; Morelos Pineda, A; Reyes-Santos, M A; Krofcheck, D; Bell, A J; Butler, P H; Doesburg, R; Reucroft, S; Silverwood, H; Ahmad, M; Asghar, M I; Butt, J; Hoorani, H R; Khan, W A; Khurshid, T; Qazi, S; Shah, M A; Shoaib, M; Bialkowska, H; Boimska, B; Frueboes, T; Górski, M; Kazana, M; Nawrocki, K; Romanowska-Rybinska, K; Szleper, M; Wrochna, G; Zalewski, P; Brona, G; Bunkowski, K; Cwiok, M; Dominik, W; Doroba, K; Kalinowski, A; Konecki, M; Krolikowski, J; Misiura, M; Wolszczak, W; Almeida, N; Bargassa, P; David, A; Faccioli, P; Ferreira Parracho, P G; Gallinaro, M; Rodrigues Antunes, J; Seixas, J; Varela, J; Vischia, P; Gavrilenko, M; Golutvin, I; Karjavin, V; Konoplyanikov, V; Korenkov, V; Kozlov, G; Lanev, A; Malakhov, A; Matveev, V; Moisenz, P; Palichik, V; Perelygin, V; Shmatov, S; Shulha, S; Skatchkov, N; Smirnov, V; Tikhonenko, E; Zarubin, A; Evstyukhin, S; Golovtsov, V; Ivanov, Y; Kim, V; Levchenko, P; Murzin, V; Oreshkin, V; Smirnov, I; Sulimov, V; Uvarov, L; Vavilov, S; Vorobyev, A; Vorobyev, An; Andreev, Yu; Dermenev, A; Gninenko, S; Golubev, N; Kirsanov, M; Krasnikov, N; Pashenkov, A; Tlisov, D; Toropin, A; Epshteyn, V; Erofeeva, M; Gavrilov, V; Lychkovskaya, N; Popov, V; Safronov, G; Semenov, S; Spiridonov, A; Stolin, V; Vlasov, E; Zhokin, A; Andreev, V; Azarkin, M; Dremin, I; Kirakosyan, M; Leonidov, A; Mesyats, G; Rusakov, S V; Vinogradov, A; Belyaev, A; Boos, E; Dubinin, M; Dudko, L; Ershov, A; Gribushin, A; Klyukhin, V; Kodolova, O; Lokhtin, I; Markina, A; Obraztsov, S; Petrushanko, S; Savrin, V; Snigirev, A; Azhgirey, I; Bayshev, I; Bitioukov, S; Kachanov, V; Kalinin, A; Konstantinov, D; Krychkine, V; Petrov, V; Ryutin, R; Sobol, A; Tourtchanovitch, L; Troshin, S; Tyurin, N; Uzunian, A; Volkov, A; Adzic, P; Djordjevic, M; Ekmedzic, M; Krpic, D; Milosevic, J; Aguilar-Benitez, M; Alcaraz Maestre, J; Battilana, C; Calvo, E; Cerrada, M; Chamizo Llatas, M; Colino, N; De La Cruz, B; Delgado Peris, A; Domínguez Vázquez, D; Fernandez Bedoya, C; Fernández Ramos, J P; Ferrando, A; Flix, J; Fouz, M C; Garcia-Abia, P; Gonzalez Lopez, O; Goy Lopez, S; Hernandez, J M; Josa, M I; Merino, G; Navarro De Martino, E; Puerta Pelayo, J; Quintario Olmeda, A; Redondo, I; Romero, L; Santaolalla, J; Soares, M S; Willmott, C; Albajar, C; de Trocóniz, J F; Brun, H; Cuevas, J; Fernandez Menendez, J; Folgueras, S; Gonzalez Caballero, I; Lloret Iglesias, L; Piedra Gomez, J; Brochero Cifuentes, J A; Cabrillo, I J; Calderon, A; Chuang, S H; Duarte Campderros, J; Fernandez, M; Gomez, G; Gonzalez Sanchez, J; Graziano, A; Jorda, C; Lopez Virto, A; Marco, J; Marco, R; Martinez Rivero, C; Matorras, F; Munoz Sanchez, F J; Rodrigo, T; Rodríguez-Marrero, A Y; Ruiz-Jimeno, A; Scodellaro, L; Vila, I; Vilar Cortabitarte, R; Abbaneo, D; Auffray, E; Auzinger, G; Bachtis, M; Baillon, P; Ball, A H; Barney, D; Bendavid, J; Benitez, J F; Bernet, C; Bianchi, G; Bloch, P; Bocci, A; Bonato, A; Bondu, O; Botta, C; Breuker, H; Camporesi, T; Cerminara, G; Christiansen, T; Coarasa Perez, J A; Colafranceschi, S; d'Enterria, D; Dabrowski, A; De Roeck, A; De Visscher, S; Di Guida, S; Dobson, M; Dupont-Sagorin, N; Elliott-Peisert, A; Eugster, J; Funk, W; Georgiou, G; Giffels, M; Gigi, D; Gill, K; Giordano, D; Girone, M; Giunta, M; Glege, F; Gomez-Reino Garrido, R; Gowdy, S; Guida, R; Hammer, J; Hansen, M; Harris, P; Hartl, C; Hegner, B; Hinzmann, A; Innocente, V; Janot, P; Karavakis, E; Kousouris, K; Krajczar, K; Lecoq, P; Lee, Y-J; Lourenço, C; Magini, N; Malberti, M; Malgeri, L; Mannelli, M; Masetti, L; Meijers, F; Mersi, S; Meschi, E; Moser, R; Mulders, M; Musella, P; Nesvold, E; Orsini, L; Palencia Cortezon, E; Perez, E; Perrozzi, L; Petrilli, A; Pfeiffer, A; Pierini, M; Pimiä, M; Piparo, D; Polese, G; Quertenmont, L; Racz, A; Reece, W; Rolandi, G; Rovelli, C; Rovere, M; Sakulin, H; Santanastasio, F; Schäfer, C; Schwick, C; Segoni, I; Sekmen, S; Sharma, A; Siegrist, P; Silva, P; Simon, M; Sphicas, P; Spiga, D; Stoye, M; Tsirou, A; Veres, G I; Vlimant, J R; Wöhri, H K; Worm, S D; Zeuner, W D; Bertl, W; Deiters, K; Erdmann, W; Gabathuler, K; Horisberger, R; Ingram, Q; Kaestli, H C; König, S; Kotlinski, D; Langenegger, U; Renker, D; Rohe, T; Bachmair, F; Bäni, L; Bortignon, P; Buchmann, M A; Casal, B; Chanon, N; Deisher, A; Dissertori, G; Dittmar, M; Donegà, M; Dünser, M; Eller, P; Freudenreich, K; Grab, C; Hits, D; Lecomte, P; Lustermann, W; Marini, A C; Martinez Ruiz Del Arbol, P; Mohr, N; Moortgat, F; Nägeli, C; Nef, P; Nessi-Tedaldi, F; Pandolfi, F; Pape, L; Pauss, F; Peruzzi, M; Ronga, F J; Rossini, M; Sala, L; Sanchez, A K; Starodumov, A; Stieger, B; Takahashi, M; Tauscher, L; Thea, A; Theofilatos, K; Treille, D; Urscheler, C; Wallny, R; Weber, H A; Amsler, C; Chiochia, V; Favaro, C; Ivova Rikova, M; Kilminster, B; Millan Mejias, B; Otiougova, P; Robmann, P; Snoek, H; Taroni, S; Tupputi, S; Verzetti, M; Cardaci, M; Chen, K H; Ferro, C; Kuo, C M; Li, S W; Lin, W; Lu, Y J; Volpe, R; Yu, S S; Bartalini, P; Chang, P; Chang, Y H; Chang, Y W; Chao, Y; Chen, K F; Dietz, C; Grundler, U; Hou, W-S; Hsiung, Y; Kao, K Y; Lei, Y J; Lu, R-S; Majumder, D; Petrakou, E; Shi, X; Shiu, J G; Tzeng, Y M; Wang, M; Asavapibhop, B; Suwonjandee, N; Adiguzel, A; Bakirci, M N; Cerci, S; Dozen, C; Dumanoglu, I; Eskut, E; Girgis, S; Gokbulut, G; Gurpinar, E; Hos, I; Kangal, E E; Kayis Topaksu, A; Onengut, G; Ozdemir, K; Ozturk, S; Polatoz, A; Sogut, K; Sunar Cerci, D; Tali, B; Topakli, H; Vergili, M; Akin, I V; Aliev, T; Bilin, B; Bilmis, S; Deniz, M; Gamsizkan, H; Guler, A M; Karapinar, G; Ocalan, K; Ozpineci, A; Serin, M; Sever, R; Surat, U E; Yalvac, M; Zeyrek, M; Gülmez, E; Isildak, B; Kaya, M; Kaya, O; Ozkorucuklu, S; Sonmez, N; Bahtiyar, H; Barlas, E; Cankocak, K; Günaydin, Y O; Vardarlı, F I; Yücel, M; Levchuk, L; Sorokin, P; Brooke, J J; Clement, E; Cussans, D; Flacher, H; Frazier, R; Goldstein, J; Grimes, M; Heath, G P; Heath, H F; Kreczko, L; Metson, S; Newbold, D M; Nirunpong, K; Poll, A; Senkin, S; Smith, V J; Williams, T; Basso, L; Bell, K W; Belyaev, A; Brew, C; Brown, R M; Cockerill, D J A; Coughlan, J A; Harder, K; Harper, S; Jackson, J; Olaiya, E; Petyt, D; Radburn-Smith, B C; Shepherd-Themistocleous, C H; Tomalin, I R; Womersley, W J; Bainbridge, R; Buchmuller, O; Burton, D; Colling, D; Cripps, N; Cutajar, M; Dauncey, P; Davies, G; Della Negra, M; Ferguson, W; Fulcher, J; Futyan, D; Gilbert, A; Guneratne Bryer, A; Hall, G; Hatherell, Z; Hays, J; Iles, G; Jarvis, M; Karapostoli, G; Kenzie, M; Lane, R; Lucas, R; Lyons, L; Magnan, A-M; Marrouche, J; Mathias, B; Nandi, R; Nash, J; Nikitenko, A; Pela, J; Pesaresi, M; Petridis, K; Pioppi, M; Raymond, D M; Rogerson, S; Rose, A; Seez, C; Sharp, P; Sparrow, A; Tapper, A; Vazquez Acosta, M; Virdee, T; Wakefield, S; Wardle, N; Whyntie, T; Chadwick, M; Cole, J E; Hobson, P R; Khan, A; Kyberd, P; Leggat, D; Leslie, D; Martin, W; Reid, I D; Symonds, P; Teodorescu, L; Turner, M; Dittmann, J; Hatakeyama, K; Kasmi, A; Liu, H; Scarborough, T; Charaf, O; Cooper, S I; Henderson, C; Rumerio, P; Avetisyan, A; Bose, T; Fantasia, C; Heister, A; Lawson, P; Lazic, D; Rohlf, J; Sperka, D; St John, J; Sulak, L; Alimena, J; Bhattacharya, S; Christopher, G; Cutts, D; Demiragli, Z; Ferapontov, A; Garabedian, A; Heintz, U; Jabeen, S; Kukartsev, G; Laird, E; Landsberg, G; Luk, M; Narain, M; Segala, M; Sinthuprasith, T; Speer, T; Breedon, R; Breto, G; Calderon De La Barca Sanchez, M; Chauhan, S; Chertok, M; Conway, J; Conway, R; Cox, P T; Erbacher, R; Gardner, M; Houtz, R; Ko, W; Kopecky, A; Lander, R; Mall, O; Miceli, T; Nelson, R; Pellett, D; Ricci-Tam, F; Rutherford, B; Searle, M; Shalhout, S; Smith, J; Squires, M; Tripathi, M; Wilbur, S; Yohay, R; Andreev, V; Cline, D; Cousins, R; Erhan, S; Everaerts, P; Farrell, C; Felcini, M; Hauser, J; Ignatenko, M; Jarvis, C; Rakness, G; Schlein, P; Takasugi, E; Traczyk, P; Valuev, V; Weber, M; Babb, J; Clare, R; Dinardo, M E; Ellison, J; Gary, J W; Hanson, G; Liu, H; Long, O R; Luthra, A; Nguyen, H; Paramesvaran, S; Sturdy, J; Sumowidagdo, S; Wilken, R; Wimpenny, S; Andrews, W; Branson, J G; Cerati, G B; Cittolin, S; Evans, D; Holzner, A; Kelley, R; Lebourgeois, M; Letts, J; Macneill, I; Mangano, B; Padhi, S; Palmer, C; Petrucciani, G; Pieri, M; Sani, M; Sharma, V; Simon, S; Sudano, E; Tadel, M; Tu, Y; Vartak, A; Wasserbaech, S; Würthwein, F; Yagil, A; Yoo, J; Barge, D; Bellan, R; Campagnari, C; D'Alfonso, M; Danielson, T; Flowers, K; Geffert, P; George, C; Golf, F; Incandela, J; Justus, C; Kalavase, P; Kovalskyi, D; Krutelyov, V; Lowette, S; Magaña Villalba, R; Mccoll, N; Pavlunin, V; Ribnik, J; Richman, J; Rossin, R; Stuart, D; To, W; West, C; Apresyan, A; Bornheim, A; Bunn, J; Chen, Y; Di Marco, E; Duarte, J; Kcira, D; Ma, Y; Mott, A; Newman, H B; Rogan, C; Spiropulu, M; Timciuc, V; Veverka, J; Wilkinson, R; Xie, S; Yang, Y; Zhu, R Y; Azzolini, V; Calamba, A; Carroll, R; Ferguson, T; Iiyama, Y; Jang, D W; Liu, Y F; Paulini, M; Russ, J; Vogel, H; Vorobiev, I; Cumalat, J P; Drell, B R; Ford, W T; Gaz, A; Luiggi Lopez, E; Nauenberg, U; Smith, J G; Stenson, K; Ulmer, K A; Wagner, S R; Alexander, J; Chatterjee, A; Eggert, N; Gibbons, L K; Hopkins, W; Khukhunaishvili, A; Kreis, B; Mirman, N; Nicolas Kaufman, G; Patterson, J R; Ryd, A; Salvati, E; Sun, W; Teo, W D; Thom, J; Thompson, J; Tucker, J; Weng, Y; Winstrom, L; Wittich, P; Winn, D; Abdullin, S; Albrow, M; Anderson, J; Apollinari, G; Bauerdick, L A T; Beretvas, A; Berryhill, J; Bhat, P C; Burkett, K; Butler, J N; Chetluru, V; Cheung, H W K; Chlebana, F; Cihangir, S; Elvira, V D; Fisk, I; Freeman, J; Gao, Y; Gottschalk, E; Gray, L; Green, D; Gutsche, O; Hare, D; Harris, R M; Hirschauer, J; Hooberman, B; Jindariani, S; Johnson, M; Joshi, U; Klima, B; Kunori, S; Kwan, S; Linacre, J; Lincoln, D; Lipton, R; Lykken, J; Maeshima, K; Marraffino, J M; Martinez Outschoorn, V I; Maruyama, S; Mason, D; McBride, P; Mishra, K; Mrenna, S; Musienko, Y; Newman-Holmes, C; O'Dell, V; Prokofyev, O; Ratnikova, N; Sexton-Kennedy, E; Sharma, S; Spalding, W J; Spiegel, L; Taylor, L; Tkaczyk, S; Tran, N V; Uplegger, L; Vaandering, E W; Vidal, R; Whitmore, J; Wu, W; Yang, F; Yun, J C; Acosta, D; Avery, P; Bourilkov, D; Chen, M; Cheng, T; Das, S; De Gruttola, M; Di Giovanni, G P; Dobur, D; Drozdetskiy, A; Field, R D; Fisher, M; Fu, Y; Furic, I K; Hugon, J; Kim, B; Konigsberg, J; Korytov, A; Kropivnitskaya, A; Kypreos, T; Low, J F; Matchev, K; Milenovic, P; Mitselmakher, G; Muniz, L; Remington, R; Rinkevicius, A; Skhirtladze, N; Snowball, M; Yelton, J; Zakaria, M; Gaultney, V; Hewamanage, S; Lebolo, L M; Linn, S; Markowitz, P; Martinez, G; Rodriguez, J L; Adams, T; Askew, A; Bochenek, J; Chen, J; Diamond, B; Gleyzer, S V; Haas, J; Hagopian, S; Hagopian, V; Johnson, K F; Prosper, H; Veeraraghavan, V; Weinberg, M; Baarmand, M M; Dorney, B; Hohlmann, M; Kalakhety, H; Yumiceva, F; Adams, M R; Apanasevich, L; Bazterra, V E; Betts, R R; Bucinskaite, I; Callner, J; Cavanaugh, R; Evdokimov, O; Gauthier, L; Gerber, C E; Hofman, D J; Khalatyan, S; Kurt, P; Lacroix, F; Moon, D H; O'Brien, C; Silkworth, C; Strom, D; Turner, P; Varelas, N; Akgun, U; Albayrak, E A; Bilki, B; Clarida, W; Dilsiz, K; Duru, F; Griffiths, S; Merlo, J-P; Mermerkaya, H; Mestvirishvili, A; Moeller, A; Nachtman, J; Newsom, C R; Ogul, H; Onel, Y; Ozok, F; Sen, S; Tan, P; Tiras, E; Wetzel, J; Yetkin, T; Yi, K; Barnett, B A; Blumenfeld, B; Bolognesi, S; Fehling, D; Giurgiu, G; Gritsan, A V; Hu, G; Maksimovic, P; Swartz, M; Whitbeck, A; Baringer, P; Bean, A; Benelli, G; Kenny, R P; Murray, M; Noonan, D; Sanders, S; Stringer, R; Wood, J S; Barfuss, A F; Chakaberia, I; Ivanov, A; Khalil, S; Makouski, M; Maravin, Y; Shrestha, S; Svintradze, I; Gronberg, J; Lange, D; Rebassoo, F; Wright, D; Baden, A; Calvert, B; Eno, S C; Gomez, J A; Hadley, N J; Kellogg, R G; Kolberg, T; Lu, Y; Marionneau, M; Mignerey, A C; Pedro, K; Peterman, A; Skuja, A; Temple, J; Tonjes, M B; Tonwar, S C; Apyan, A; Bauer, G; Busza, W; Butz, E; Cali, I A; Chan, M; Dutta, V; Gomez Ceballos, G; Goncharov, M; Kim, Y; Klute, M; Lai, Y S; Levin, A; Luckey, P D; Ma, T; Nahn, S; Paus, C; Ralph, D; Roland, C; Roland, G; Stephans, G S F; Stöckli, F; Sumorok, K; Sung, K; Velicanu, D; Wolf, R; Wyslouch, B; Yang, M; Yilmaz, Y; Yoon, A S; Zanetti, M; Zhukova, V; Dahmes, B; De Benedetti, A; Franzoni, G; Gude, A; Haupt, J; Kao, S C; Klapoetke, K; Kubota, Y; Mans, J; Pastika, N; Rusack, R; Sasseville, M; Singovsky, A; Tambe, N; Turkewitz, J; Cremaldi, L M; Kroeger, R; Perera, L; Rahmat, R; Sanders, D A; Summers, D; Avdeeva, E; Bloom, K; Bose, S; Claes, D R; Dominguez, A; Eads, M; Gonzalez Suarez, R; Keller, J; Kravchenko, I; Lazo-Flores, J; Malik, S; Meier, F; Snow, G R; Dolen, J; Godshalk, A; Iashvili, I; Jain, S; Kharchilava, A; Kumar, A; Rappoccio, S; Wan, Z; Alverson, G; Barberis, E; Baumgartel, D; Chasco, M; Haley, J; Nash, D; Orimoto, T; Trocino, D; Wood, D; Zhang, J; Anastassov, A; Hahn, K A; Kubik, A; Lusito, L; Mucia, N; Odell, N; Pollack, B; Pozdnyakov, A; Schmitt, M; Stoynev, S; Velasco, M; Won, S; Berry, D; Brinkerhoff, A; Chan, K M; Hildreth, M; Jessop, C; Karmgard, D J; Kolb, J; Lannon, K; Luo, W; Lynch, S; Marinelli, N; Morse, D M; Pearson, T; Planer, M; Ruchti, R; Slaunwhite, J; Valls, N; Wayne, M; Wolf, M; Antonelli, L; Bylsma, B; Durkin, L S; Hill, C; Hughes, R; Kotov, K; Ling, T Y; Puigh, D; Rodenburg, M; Smith, G; Vuosalo, C; Williams, G; Winer, B L; Wolfe, H; Berry, E; Elmer, P; Halyo, V; Hebda, P; Hegeman, J; Hunt, A; Jindal, P; Koay, S A; Lopes Pegna, D; Lujan, P; Marlow, D; Medvedeva, T; Mooney, M; Olsen, J; Piroué, P; Quan, X; Raval, A; Saka, H; Stickland, D; Tully, C; Werner, J S; Zenz, S C; Zuranski, A; Brownson, E; Lopez, A; Mendez, H; Ramirez Vargas, J E; Alagoz, E; Benedetti, D; Bolla, G; Bortoletto, D; De Mattia, M; Everett, A; Hu, Z; Jones, M; Jung, K; Koybasi, O; Kress, M; Leonardo, N; Maroussov, V; Merkel, P; Miller, D H; Neumeister, N; Shipsey, I; Silvers, D; Svyatkovskiy, A; Vidal Marono, M; Wang, F; Xu, L; Yoo, H D; Zablocki, J; Zheng, Y; Guragain, S; Parashar, N; Adair, A; Akgun, B; Ecklund, K M; Geurts, F J M; Li, W; Padley, B P; Redjimi, R; Roberts, J; Zabel, J; Betchart, B; Bodek, A; Covarelli, R; de Barbaro, P; Demina, R; Eshaq, Y; Ferbel, T; Garcia-Bellido, A; Goldenzweig, P; Han, J; Harel, A; Miner, D C; Petrillo, G; Vishnevskiy, D; Zielinski, M; Bhatti, A; Ciesielski, R; Demortier, L; Goulianos, K; Lungu, G; Malik, S; Mesropian, C; Arora, S; Barker, A; Chou, J P; Contreras-Campana, C; Contreras-Campana, E; Duggan, D; Ferencek, D; Gershtein, Y; Gray, R; Halkiadakis, E; Hidas, D; Lath, A; Panwalkar, S; Park, M; Patel, R; Rekovic, V; Robles, J; Rose, K; Salur, S; Schnetzer, S; Seitz, C; Somalwar, S; Stone, R; Thomas, S; Walker, M; Cerizza, G; Hollingsworth, M; Spanier, S; Yang, Z C; York, A; Bouhali, O; Eusebi, R; Flanagan, W; Gilmore, J; Kamon, T; Khotilovich, V; Montalvo, R; Osipenkov, I; Pakhotin, Y; Perloff, A; Roe, J; Safonov, A; Sakuma, T; Suarez, I; Tatarinov, A; Toback, D; Akchurin, N; Damgov, J; Dragoiu, C; Dudero, P R; Jeong, C; Kovitanggoon, K; Lee, S W; Libeiro, T; Volobouev, I; Appelt, E; Delannoy, A G; Greene, S; Gurrola, A; Johns, W; Maguire, C; Mao, Y; Melo, A; Sharma, M; Sheldon, P; Snook, B; Tuo, S; Velkovska, J; Arenton, M W; Boutle, S; Cox, B; Francis, B; Goodell, J; Hirosky, R; Ledovskoy, A; Lin, C; Neu, C; Wood, J; Gollapinni, S; Harr, R; Karchin, P E; Kottachchi Kankanamge Don, C; Lamichhane, P; Sakharov, A; Anderson, M; Belknap, D A; Borrello, L; Carlsmith, D; Cepeda, M; Dasu, S; Friis, E; Grogg, K S; Grothe, M; Hall-Wilton, R; Herndon, M; Hervé, A; Kaadze, K; Klabbers, P; Klukas, J; Lanaro, A; Lazaridis, C; Loveless, R; Mohapatra, A; Mozer, M U; Ojalvo, I; Pierro, G A; Ross, I; Savin, A; Smith, W H; Swanson, J

2014-05-16

A measurement of total and fiducial inclusive W and Z boson production cross sections in pp collisions at sqrt[s] = 8 TeV is presented. Electron and muon final states are analyzed in a data sample collected with the CMS detector corresponding to an integrated luminosity of 18.2 ± 0.5 pb(-1). The measured total inclusive cross sections times branching fractions are σ(pp → WX)×B(W → ℓν) = 12.21 ± 0.03(stat) ± 0.24(syst) ± 0.32(lum) nb and σ(pp → ZX) × B(Z → ℓ+ℓ-) = 1.15 ± 0.01(stat) ± 0.02(syst) ± 0.03(lum) nb for the dilepton mass in the range of 60-120 GeV. The measured values agree with next-to-next-to-leading-order QCD cross section calculations. Ratios of cross sections are reported with a precision of 2%. This is the first measurement of inclusive W and Z boson production in proton-proton collisions at sqrt[s] = 8 TeV.

Carfilzomib induces leukaemia cell apoptosis via inhibiting ELK1/KIAA1524 (Elk-1/CIP2A) and activating PP2A not related to proteasome inhibition.

PubMed

Liu, Chun-Yu; Hsieh, Feng-Shu; Chu, Pei-Yi; Tsai, Wen-Chun; Huang, Chun-Teng; Yu, Yuan-Bin; Huang, Tzu-Ting; Ko, Po-Shen; Hung, Man-Hsin; Wang, Wan-Lun; Shiau, Chung-Wai; Chen, Kuen-Feng

2017-06-01

Enhancing the tumour suppressive activity of protein phosphatase 2A (PP2A) has been suggested to be an anti-leukaemic strategy. KIAA1524 (also termed CIP2A), an oncoprotein inhibiting PP2A, is associated with disease progression in chronic myeloid leukaemia and may be prognostic in cytogenetically normal acute myeloid leukaemia. Here we demonstrated that the selective proteasome inhibitor, carfilzomib, induced apoptosis in sensitive primary leukaemia cells and in sensitive leukaemia cell lines, associated with KIAA1524 protein downregulation, increased PP2A activity and decreased p-Akt, but not with the proteasome inhibition effect of carfilzomib. Ectopic expression of KIAA1524, or pretreatment with the PP2A inhibitor, okadaic acid, suppressed carfilzomib-induced apoptosis and KIAA1524 downregulation in sensitive cells, whereas co-treatment with the PP2A agonist, forskolin, enhanced carfilzomib-induced apoptosis in resistant cells. Mechanistically, carfilzomib affected KIAA1524 transcription through disturbing ELK1 (Elk-1) binding to the KIAA1524 promoter. Moreover, the drug sensitivity and mechanism of carfilzomib in xenograft mouse models correlated well with the effects of carfilzomib on KIAA1524 and p-Akt expression, as well as PP2A activity. Our data disclosed a novel drug mechanism of carfilzomib in leukaemia cells and suggests the potential therapeutic implication of KIAA1524 in leukaemia treatment. © 2017 John Wiley & Sons Ltd.

Location of intense electromagnetic ion cyclotron (EMIC) wave events relative to the plasmapause: Van Allen Probes observations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tetrick, S. S.; Engebretson, M. J.; Posch, J. L.

In this paper, we have studied the spatial location relative to the plasmapause (PP) of the most intense electromagnetic ion cyclotron (EMIC) waves observed on Van Allen Probes A and B during their first full precession in local time. Most of these waves occurred over an L range of from -1 to +2 R E relative to the PP. Very few events occurred only within 0.1 R E of the PP, and events with a width in L of < 0.2 R E occurred both inside and outside the PP. Wave occurrence was always associated with high densities of ringmore » current ions; plasma density gradients or enhancements were associated with some events but were not dominant factors in determining the sites of wave generation. Storm main and recovery phase events in the dusk sector were often inside the PP, and dayside events during quiet times and compressions of the magnetosphere were more evenly distributed both inside and outside the PP. Superposed epoch analyses of the dependence of wave onset on solar wind dynamic pressure (Psw), the SME (SuperMAG auroral electrojet) index, and the SYM-H index showed that substorm injections and solar wind compressions were temporally closely associated with EMIC wave onset but to an extent that varied with frequency band, magnetic local time, and storm phase, and location relative to the PP. Finally, the fact that increases in SME and Psw were less strongly correlated with events at the PP than with other events might suggest that the occurrence of those events was affected by the density gradient.« less

Location of intense electromagnetic ion cyclotron (EMIC) wave events relative to the plasmapause: Van Allen Probes observations

DOE PAGES

Tetrick, S. S.; Engebretson, M. J.; Posch, J. L.; ...

2017-03-17

In this paper, we have studied the spatial location relative to the plasmapause (PP) of the most intense electromagnetic ion cyclotron (EMIC) waves observed on Van Allen Probes A and B during their first full precession in local time. Most of these waves occurred over an L range of from -1 to +2 R E relative to the PP. Very few events occurred only within 0.1 R E of the PP, and events with a width in L of < 0.2 R E occurred both inside and outside the PP. Wave occurrence was always associated with high densities of ringmore » current ions; plasma density gradients or enhancements were associated with some events but were not dominant factors in determining the sites of wave generation. Storm main and recovery phase events in the dusk sector were often inside the PP, and dayside events during quiet times and compressions of the magnetosphere were more evenly distributed both inside and outside the PP. Superposed epoch analyses of the dependence of wave onset on solar wind dynamic pressure (Psw), the SME (SuperMAG auroral electrojet) index, and the SYM-H index showed that substorm injections and solar wind compressions were temporally closely associated with EMIC wave onset but to an extent that varied with frequency band, magnetic local time, and storm phase, and location relative to the PP. Finally, the fact that increases in SME and Psw were less strongly correlated with events at the PP than with other events might suggest that the occurrence of those events was affected by the density gradient.« less

Impacts of dietary calcium, phytate, and nonphytate phosphorus concentrations in the presence or absence of phytase on inositol hexakisphosphate (IP6) degradation in different segments of broilers digestive tract.

PubMed

Li, W; Angel, R; Kim, S-W; Brady, K; Yu, S; Plumstead, P W

2016-03-01

A total of 1,440 straight-run Heritage 56M × fast-feathering Cobb 500F broiler birds were fed from 11 to 13 d of age to determine the impacts of calcium (Ca), phytate phosphorus (PP), nonphytate P (NPP) and phytase concentrations on the myo-inositol hexakisphosphate (IP6) flow through the different parts of gastrointestinal tract (GIT). The experiment was a 2×2×2×3 randomized block design with 2 Ca (0.7 and 1.0%), 2 PP (0.23 and 0.34%), 2 nPP (0.28 and 0.45%) and 3 phytase (0-, 500-, and 1,000-phytase unit (FTU)/kg) concentrations. The experiment was replicated twice (block) with 3 replicates per treatment (TRT) of 10 birds per block. Concentration of IP6 in crop, proventriculus (PROV) plus (+) gizzard (GIZ) and distal ileum digesta as well as the ileal IP6 disappearance was determined at 13 d of age. In crop, higher IP6 concentration was seen with increased Ca (P < 0.05). Despite the interaction between PP and phytase, higher dietary PP led to greater IP6 concentration (P < 0.05). Similar main effects of PP and phytase were also seen in Prov+Giz and ileum (P < 0.05) without interactions. Interaction between Ca and nPP on IP6 concentration was seen in Prov+Giz (P < 0.05). Decreased ileal IP6 disappearance was found at higher Ca (62.3% at 0.7% Ca vs. 57.5% at 1.0% Ca; P < 0.05). In general, adding phytase improved IP6 degradation but the degree of impact was dependent on nPP and PP (P < 0.05). In conclusion, phytase inclusion significantly reduced IP6 concentration and IP6 disappearance in distal ileum regardless of GIT segments or diet composition, but impacts of dietary Ca, nPP, and PP differed depending on GIT segment examined. © The Author 2016. Published by Oxford University Press on behalf of Poultry Science Association.

The Psen1-L166P-knock-in mutation leads to amyloid deposition in human wild-type amyloid precursor protein YAC transgenic mice

PubMed Central

Vidal, Ruben; Sammeta, Neeraja; Garringer, Holly J.; Sambamurti, Kumar; Miravalle, Leticia; Lamb, Bruce T.; Ghetti, Bernardino

2012-01-01

Genetically engineered mice have been generated to model cerebral β-amyloidosis, one of the hallmarks of Alzheimer disease (AD) pathology, based on the overexpression of a mutated cDNA of the amyloid-β precursor protein (AβPP) or by knock-in of the murine Aβpp gene alone or with presenilin1 mutations. Here we describe the generation and initial characterization of a new mouse line based on the presence of 2 copies of the human genomic region encoding the wild-type AβPP and the L166P presenilin 1 mutation. At ∼6 mo of age, double-mutant mice develop amyloid pathology, with signs of neuritic dystrophy, intracellular Aβ accumulation, and glial inflammation, an increase in AβPP C-terminal fragments, and an 8 times increase in Aβ42 levels with a 40% decrease in Aβ40 levels, leading to a significant increase (14 times) of Aβ42/Aβ40 ratios, with minimal effects on presenilin or the Notch1 pathway in the brain. We conclude that in mice, neither mutations in AβPP nor overexpression of an AβPP isoform are a prerequisite for Aβ pathology. This model will allow the study of AD pathogenesis and testing of therapeutic strategies in a more relevant environment without experimental artifacts due to the overexpression of a single-mutant AβPP isoform using exogenous promoters.—Vidal, R., Sammeta, N., Garringer, H. J., Sambamurti, K., Miravalle, L., Lamb B. T., Ghetti, B. The Psen1-L166P-knock-in mutation leads to amyloid deposition in human wild-type amyloid precursor protein YAC transgenic mice. PMID:22459153

Factors Affecting Pro- and Anti-Oxidant Properties of Fragments of the b-Protein Precursor (bPP): Implication for Alzheimer's Disease.

PubMed

Andorn, Anne C.; Kalaria, Rajesh N.

2000-06-01

Oxidative stress may have a key pathogenetic role in neurodegenerative diseases including Alzheimer's disease (AD). While there is evidence that some amyloid-b (Ab) peptides can initiate oxidative stress at micromolar doses, there is also some evidence that oxidative stress increases the concentration of the b-protein precursor (bPP) and the potential for increased formation of the Ab peptides. The following studies were performed to test the hypothesis that fragments of bPP could be antioxidants and hence that oxidative stress might be an early event in AD. We found that several fragments of bPP, including the Ab peptides, inhibit ascorbate-stimulated lipid peroxidation (ASLP) in membrane fragment preparations of postmortem human brain. In contrast, other fragments of bPP enhance ASLP. These data indicate that bPP or fragments of bPP could play a key role in the redox status of cells and that alterations in bPP processing could have profound effects on the cellular response to oxidative stress.

Interactions of ABA signaling core components (SlPYLs, SlPP2Cs, and SlSnRK2s) in tomato (Solanum lycopersicon).

PubMed

Chen, Pei; Sun, Yu-Fei; Kai, Wen-Bin; Liang, Bin; Zhang, Yu-Shu; Zhai, Xia-Wan; Jiang, Li; Du, Yang-Wei; Leng, Ping

2016-10-20

Abscisic acid (ABA) regulates fruit development and ripening via its signaling. However, the exact role of ABA signaling core components in fruit have not yet been clarified. In this study, we investigated the potential interactions of tomato (Solanum lycopersicon) ABA signaling core components using yeast two-hybrid analysis, with or without ABA at different concentrations. The results showed that among 12 PYR/PYL/RCAR ABA receptors (SlPYLs), SlPYL1, SlPYL2, SlPYL4, SlPYL5, SlPYL 7, SlPYL8, SlPYL9, SlPYL10, SlPYL11, and SlPYL13 were ABA-dependent receptors, while SlPYL3 and SlPYL12 were ABA-independent receptors. Among five SlPP2Cs (type 2C protein phosphatases) and seven SlSnRK2s (subfamily 2 of SNF1-related kinases), all SlSnRK2s could interact with SlPP2C2, while SlSnRK2.8 also interacted with SlPP2C3. SlSnRK2.5 could interact with SlABF2/4 (ABA-responsive element binding factors). Expressions of SlPYL1, SlPYL2, SlPYL8, and SlPYL10 were upregulated under exogenous ABA but downregulated under nordihydroguaiaretic acid (NDGA) at the mature green stage of fruit ripening. The expressions of SlPP2C1, SlPP2C2, SlPP2C3, and SlPP2C5 were upregulated in ABA-treated fruit, but downregulated in NDGA-treated fruit at the mature green stage. The expressions of SlSnRK2.4, SlSnRK2.5, SlSnRK2.6, and SlSnRK2.7 were upregulated by ABA, but downregulated by NDGA. However, SlSnRK2.2 was down regulated by ABA. Expression of SlABF2/3/4 was enhanced by ABA but decreased by NDGA. Based on these results, we concluded that the majority of ABA receptor PYLs interact with SlPP2Cs in an ABA-dependent manner. SlPP2C2 and SlPP2C3 can interact with SlSnRK2s. SlSnRK2.5 could interact with SlABF2/4. Most ABA signaling core components respond to exogenous ABA. Copyright © 2016 Elsevier GmbH. All rights reserved.

Predictive MRI correlates of lesser metatarsophalangeal joint plantar plate tear.

PubMed

Umans, Rachel L; Umans, Benjamin D; Umans, Hilary; Elsinger, Elisabeth

2016-07-01

To identify correlated signs on non-enhanced MRI that might improve diagnostic detection of plantar plate (PP) tear. We performed an IRB-approved, HIPAA-compliant retrospective analysis of 100 non-contrast MRI (50 PP tear, 50 controls). All were anonymized, randomized, and reviewed; 20 were duplicated to assess consistency. One musculoskeletal radiologist evaluated qualitative variables. A trained non-physician performed measurements. Consistency and concordance were assessed. Pearson's Chi-square test was used to test the correlation between qualitative findings and PP tear status. Correlation between measurements and PP status was assessed using t tests and Wilcoxon's rank-sum test (p values < 0.05 considered significant). Classification and regression trees were utilized to identify attributes that, taken together, would consistently distinguish PP tear from controls. Quantitative measurements were highly reproducible (concordance 0.88-0.99). Elevated 2nd MT protrusion, lesser MT supination and rotational divergence of >45° between the 1st-2nd MT axis correlated with PP tear. Pericapsular soft tissue thickening correlated most strongly with PP tear, correctly classifying 95 % of cases and controls. Excluding pericapsular soft tissue thickening, sequential assessment of 2nd toe enthesitis, 2nd flexor tendon subluxation, and splaying of the second and third toes accurately classified PP status in 92 %. Pericapsular soft tissue thickening most strongly correlated with PP tear. For cases in which it might be difficult to distinguish pericapsular fibrosis from neuroma, sequential assessment of 2nd toe enthesitis, flexor tendon subluxation and splaying of the 2nd and 3rd toe is most helpful for optimizing accurate diagnosis of PP tear.

First observation of forward Z → b b bar production in pp collisions at √{ s } = 8 TeV

NASA Astrophysics Data System (ADS)

Aaij, R.; Adeva, B.; Adinolfi, M.; Ajaltouni, Z.; Akar, S.; Albrecht, J.; Alessio, F.; Alexander, M.; Alfonso Albero, A.; Ali, S.; Alkhazov, G.; Alvarez Cartelle, P.; Alves, A. A.; Amato, S.; Amerio, S.; Amhis, Y.; An, L.; Anderlini, L.; Andreassi, G.; Andreotti, M.; Andrews, J. E.; Appleby, R. B.; Archilli, F.; d'Argent, P.; Arnau Romeu, J.; Artamonov, A.; Artuso, M.; Aslanides, E.; Auriemma, G.; Baalouch, M.; Babuschkin, I.; Bachmann, S.; Back, J. J.; Badalov, A.; Baesso, C.; Baker, S.; Balagura, V.; Baldini, W.; Baranov, A.; Barlow, R. J.; Barschel, C.; Barsuk, S.; Barter, W.; Baryshnikov, F.; Batozskaya, V.; Battista, V.; Bay, A.; Beaucourt, L.; Beddow, J.; Bedeschi, F.; Bediaga, I.; Beiter, A.; Bel, L. J.; Beliy, N.; Bellee, V.; Belloli, N.; Belous, K.; Belyaev, I.; Ben-Haim, E.; Bencivenni, G.; Benson, S.; Beranek, S.; Berezhnoy, A.; Bernet, R.; Berninghoff, D.; Bertholet, E.; Bertolin, A.; Betancourt, C.; Betti, F.; Bettler, M.-O.; van Beuzekom, M.; Bezshyiko, Ia.; Bifani, S.; Billoir, P.; Birnkraut, A.; Bitadze, A.; Bizzeti, A.; Bjørn, M.; Blake, T.; Blanc, F.; Blouw, J.; Blusk, S.; Bocci, V.; Boettcher, T.; Bondar, A.; Bondar, N.; Bonivento, W.; Bordyuzhin, I.; Borgheresi, A.; Borghi, S.; Borisyak, M.; Borsato, M.; Bossu, F.; Boubdir, M.; Bowcock, T. J. V.; Bowen, E.; Bozzi, C.; Braun, S.; Britton, T.; Brodzicka, J.; Brundu, D.; Buchanan, E.; Burr, C.; Bursche, A.; Buytaert, J.; Byczynski, W.; Cadeddu, S.; Cai, H.; Calabrese, R.; Calladine, R.; Calvi, M.; Calvo Gomez, M.; Camboni, A.; Campana, P.; Campora Perez, D. H.; Capriotti, L.; Carbone, A.; Carboni, G.; Cardinale, R.; Cardini, A.; Carniti, P.; Carson, L.; Carvalho Akiba, K.; Casse, G.; Cassina, L.; Castillo Garcia, L.; Cattaneo, M.; Cavallero, G.; Cenci, R.; Chamont, D.; Chapman, M. G.; Charles, M.; Charpentier, Ph.; Chatzikonstantinidis, G.; Chefdeville, M.; Chen, S.; Cheung, S. F.; Chitic, S.-G.; Chobanova, V.; Chrzaszcz, M.; Chubykin, A.; Ciambrone, P.; Cid Vidal, X.; Ciezarek, G.; Clarke, P. E. L.; Clemencic, M.; Cliff, H. V.; Closier, J.; Cogan, J.; Cogneras, E.; Cogoni, V.; Cojocariu, L.; Collins, P.; Colombo, T.; Comerma-Montells, A.; Contu, A.; Cook, A.; Coombs, G.; Coquereau, S.; Corti, G.; Corvo, M.; Costa Sobral, C. M.; Couturier, B.; Cowan, G. A.; Craik, D. C.; Crocombe, A.; Cruz Torres, M.; Currie, R.; D'Ambrosio, C.; Da Cunha Marinho, F.; Dall'Occo, E.; Dalseno, J.; Davis, A.; De Aguiar Francisco, O.; De Capua, S.; De Cian, M.; De Miranda, J. M.; De Paula, L.; De Serio, M.; De Simone, P.; Dean, C. T.; Decamp, D.; Del Buono, L.; Dembinski, H.-P.; Demmer, M.; Dendek, A.; Derkach, D.; Deschamps, O.; Dettori, F.; Dey, B.; Di Canto, A.; Di Nezza, P.; Dijkstra, H.; Dordei, F.; Dorigo, M.; Dosil Suárez, A.; Douglas, L.; Dovbnya, A.; Dreimanis, K.; Dufour, L.; Dujany, G.; Durante, P.; Dzhelyadin, R.; Dziewiecki, M.; Dziurda, A.; Dzyuba, A.; Easo, S.; Ebert, M.; Egede, U.; Egorychev, V.; Eidelman, S.; Eisenhardt, S.; Eitschberger, U.; Ekelhof, R.; Eklund, L.; Ely, S.; Esen, S.; Evans, H. M.; Evans, T.; Falabella, A.; Farley, N.; Farry, S.; Fazzini, D.; Federici, L.; Ferguson, D.; Fernandez, G.; Fernandez Declara, P.; Fernandez Prieto, A.; Ferrari, F.; Ferreira Rodrigues, F.; Ferro-Luzzi, M.; Filippov, S.; Fini, R. A.; Fiore, M.; Fiorini, M.; Firlej, M.; Fitzpatrick, C.; Fiutowski, T.; Fleuret, F.; Fohl, K.; Fontana, M.; Fontanelli, F.; Forshaw, D. C.; Forty, R.; Franco Lima, V.; Frank, M.; Frei, C.; Fu, J.; Funk, W.; Furfaro, E.; Färber, C.; Gabriel, E.; Gallas Torreira, A.; Galli, D.; Gallorini, S.; Gambetta, S.; Gandelman, M.; Gandini, P.; Gao, Y.; Garcia Martin, L. M.; García Pardiñas, J.; Garra Tico, J.; Garrido, L.; Garsed, P. J.; Gascon, D.; Gaspar, C.; Gavardi, L.; Gazzoni, G.; Gerick, D.; Gersabeck, E.; Gersabeck, M.; Gershon, T.; Ghez, Ph.; Gianì, S.; Gibson, V.; Girard, O. G.; Giubega, L.; Gizdov, K.; Gligorov, V. V.; Golubkov, D.; Golutvin, A.; Gomes, A.; Gorelov, I. V.; Gotti, C.; Govorkova, E.; Grabowski, J. P.; Graciani Diaz, R.; Granado Cardoso, L. A.; Graugés, E.; Graverini, E.; Graziani, G.; Grecu, A.; Greim, R.; Griffith, P.; Grillo, L.; Gruber, L.; Gruberg Cazon, B. R.; Grünberg, O.; Gushchin, E.; Guz, Yu.; Gys, T.; Göbel, C.; Hadavizadeh, T.; Hadjivasiliou, C.; Haefeli, G.; Haen, C.; Haines, S. C.; Hamilton, B.; Han, X.; Hancock, T. H.; Hansmann-Menzemer, S.; Harnew, N.; Harnew, S. T.; Harrison, J.; Hasse, C.; Hatch, M.; He, J.; Hecker, M.; Heinicke, K.; Heister, A.; Hennessy, K.; Henrard, P.; Henry, L.; van Herwijnen, E.; Heß, M.; Hicheur, A.; Hill, D.; Hombach, C.; Hopchev, P. H.; Huard, Z. C.; Hulsbergen, W.; Humair, T.; Hushchyn, M.; Hutchcroft, D.; Ibis, P.; Idzik, M.; Ilten, P.; Jacobsson, R.; Jalocha, J.; Jans, E.; Jawahery, A.; Jiang, F.; John, M.; Johnson, D.; Jones, C. R.; Joram, C.; Jost, B.; Jurik, N.; Kandybei, S.; Karacson, M.; Kariuki, J. M.; Karodia, S.; Kazeev, N.; Kecke, M.; Kelsey, M.; Kenzie, M.; Ketel, T.; Khairullin, E.; Khanji, B.; Khurewathanakul, C.; Kirn, T.; Klaver, S.; Klimaszewski, K.; Klimkovich, T.; Koliiev, S.; Kolpin, M.; Komarov, I.; Kopecna, R.; Koppenburg, P.; Kosmyntseva, A.; Kotriakhova, S.; Kozeiha, M.; Kravchuk, L.; Kreps, M.; Krokovny, P.; Kruse, F.; Krzemien, W.; Kucewicz, W.; Kucharczyk, M.; Kudryavtsev, V.; Kuonen, A. K.; Kurek, K.; Kvaratskheliya, T.; Lacarrere, D.; Lafferty, G.; Lai, A.; Lanfranchi, G.; Langenbruch, C.; Latham, T.; Lazzeroni, C.; Le Gac, R.; Leflat, A.; Lefrançois, J.; Lefèvre, R.; Lemaitre, F.; Lemos Cid, E.; Leroy, O.; Lesiak, T.; Leverington, B.; Li, P.-R.; Li, T.; Li, Y.; Li, Z.; Likhomanenko, T.; Lindner, R.; Lionetto, F.; Lisovskyi, V.; Liu, X.; Loh, D.; Loi, A.; Longstaff, I.; Lopes, J. H.; Lucchesi, D.; Lucio Martinez, M.; Luo, H.; Lupato, A.; Luppi, E.; Lupton, O.; Lusiani, A.; Lyu, X.; Machefert, F.; Maciuc, F.; Macko, V.; Mackowiak, P.; Maddrell-Mander, S.; Maev, O.; Maguire, K.; Maisuzenko, D.; Majewski, M. W.; Malde, S.; Malinin, A.; Maltsev, T.; Manca, G.; Mancinelli, G.; Manning, P.; Marangotto, D.; Maratas, J.; Marchand, J. F.; Marconi, U.; Marin Benito, C.; Marinangeli, M.; Marino, P.; Marks, J.; Martellotti, G.; Martin, M.; Martinelli, M.; Martinez Santos, D.; Martinez Vidal, F.; Martins Tostes, D.; Massacrier, L. M.; Massafferri, A.; Matev, R.; Mathad, A.; Mathe, Z.; Matteuzzi, C.; Mauri, A.; Maurice, E.; Maurin, B.; Mazurov, A.; McCann, M.; McNab, A.; McNulty, R.; Mead, J. V.; Meadows, B.; Meaux, C.; Meier, F.; Meinert, N.; Melnychuk, D.; Merk, M.; Merli, A.; Michielin, E.; Milanes, D. A.; Millard, E.; Minard, M.-N.; Minzoni, L.; Mitzel, D. S.; Mogini, A.; Molina Rodriguez, J.; Mombächer, T.; Monroy, I. A.; Monteil, S.; Morandin, M.; Morello, M. J.; Morgunova, O.; Moron, J.; Morris, A. B.; Mountain, R.; Muheim, F.; Mulder, M.; Müller, D.; Müller, J.; Müller, K.; Müller, V.; Naik, P.; Nakada, T.; Nandakumar, R.; Nandi, A.; Nasteva, I.; Needham, M.; Neri, N.; Neubert, S.; Neufeld, N.; Neuner, M.; Nguyen, T. D.; Nguyen-Mau, C.; Nieswand, S.; Niet, R.; Nikitin, N.; Nikodem, T.; Nogay, A.; O'Hanlon, D. P.; Oblakowska-Mucha, A.; Obraztsov, V.; Ogilvy, S.; Oldeman, R.; Onderwater, C. J. G.; Ossowska, A.; Otalora Goicochea, J. M.; Owen, P.; Oyanguren, A.; Pais, P. R.; Palano, A.; Palutan, M.; Papanestis, A.; Pappagallo, M.; Pappalardo, L. L.; Parker, W.; Parkes, C.; Passaleva, G.; Pastore, A.; Patel, M.; Patrignani, C.; Pearce, A.; Pellegrino, A.; Penso, G.; Pepe Altarelli, M.; Perazzini, S.; Perret, P.; Pescatore, L.; Petridis, K.; Petrolini, A.; Petrov, A.; Petruzzo, M.; Picatoste Olloqui, E.; Pietrzyk, B.; Pikies, M.; Pinci, D.; Pisani, F.; Pistone, A.; Piucci, A.; Placinta, V.; Playfer, S.; Plo Casasus, M.; Polci, F.; Poli Lener, M.; Poluektov, A.; Polyakov, I.; Polycarpo, E.; Pomery, G. J.; Ponce, S.; Popov, A.; Popov, D.; Poslavskii, S.; Potterat, C.; Price, E.; Prisciandaro, J.; Prouve, C.; Pugatch, V.; Puig Navarro, A.; Pullen, H.; Punzi, G.; Qian, W.; Quagliani, R.; Quintana, B.; Rachwal, B.; Rademacker, J. H.; Rama, M.; Ramos Pernas, M.; Rangel, M. S.; Raniuk, I.; Ratnikov, F.; Raven, G.; Ravonel Salzgeber, M.; Reboud, M.; Redi, F.; Reichert, S.; dos Reis, A. C.; Remon Alepuz, C.; Renaudin, V.; Ricciardi, S.; Richards, S.; Rihl, M.; Rinnert, K.; Rives Molina, V.; Robbe, P.; Robert, A.; Rodrigues, A. B.; Rodrigues, E.; Rodriguez Lopez, J. A.; Rodriguez Perez, P.; Rogozhnikov, A.; Roiser, S.; Rollings, A.; Romanovskiy, V.; Romero Vidal, A.; Ronayne, J. W.; Rotondo, M.; Rudolph, M. S.; Ruf, T.; Ruiz Valls, P.; Ruiz Vidal, J.; Saborido Silva, J. J.; Sadykhov, E.; Sagidova, N.; Saitta, B.; Salustino Guimaraes, V.; Sanchez Mayordomo, C.; Sanmartin Sedes, B.; Santacesaria, R.; Santamarina Rios, C.; Santimaria, M.; Santovetti, E.; Sarpis, G.; Sarti, A.; Satriano, C.; Satta, A.; Saunders, D. M.; Savrina, D.; Schael, S.; Schellenberg, M.; Schiller, M.; Schindler, H.; Schlupp, M.; Schmelling, M.; Schmelzer, T.; Schmidt, B.; Schneider, O.; Schopper, A.; Schreiner, H. F.; Schubert, K.; Schubiger, M.; Schune, M.-H.; Schwemmer, R.; Sciascia, B.; Sciubba, A.; Semennikov, A.; Sepulveda, E. S.; Sergi, A.; Serra, N.; Serrano, J.; Sestini, L.; Seyfert, P.; Shapkin, M.; Shapoval, I.; Shcheglov, Y.; Shears, T.; Shekhtman, L.; Shevchenko, V.; Siddi, B. G.; Silva Coutinho, R.; Silva de Oliveira, L.; Simi, G.; Simone, S.; Sirendi, M.; Skidmore, N.; Skwarnicki, T.; Smith, E.; Smith, I. T.; Smith, J.; Smith, M.; Soares Lavra, l.; Sokoloff, M. D.; Soler, F. J. P.; Souza De Paula, B.; Spaan, B.; Spradlin, P.; Sridharan, S.; Stagni, F.; Stahl, M.; Stahl, S.; Stefko, P.; Stefkova, S.; Steinkamp, O.; Stemmle, S.; Stenyakin, O.; Stepanova, M.; Stevens, H.; Stone, S.; Storaci, B.; Stracka, S.; Stramaglia, M. E.; Straticiuc, M.; Straumann, U.; Sun, J.; Sun, L.; Sutcliffe, W.; Swientek, K.; Syropoulos, V.; Szczekowski, M.; Szumlak, T.; Szymanski, M.; T'Jampens, S.; Tayduganov, A.; Tekampe, T.; Tellarini, G.; Teubert, F.; Thomas, E.; van Tilburg, J.; Tilley, M. J.; Tisserand, V.; Tobin, M.; Tolk, S.; Tomassetti, L.; Tonelli, D.; Toriello, F.; Tourinho Jadallah Aoude, R.; Tournefier, E.; Traill, M.; Tran, M. T.; Tresch, M.; Trisovic, A.; Tsaregorodtsev, A.; Tsopelas, P.; Tully, A.; Tuning, N.; Ukleja, A.; Usachov, A.; Ustyuzhanin, A.; Uwer, U.; Vacca, C.; Vagner, A.; Vagnoni, V.; Valassi, A.; Valat, S.; Valenti, G.; Vazquez Gomez, R.; Vazquez Regueiro, P.; Vecchi, S.; van Veghel, M.; Velthuis, J. J.; Veltri, M.; Veneziano, G.; Venkateswaran, A.; Verlage, T. A.; Vernet, M.; Vesterinen, M.; Viana Barbosa, J. V.; Viaud, B.; Vieira, D.; Vieites Diaz, M.; Viemann, H.; Vilasis-Cardona, X.; Vitti, M.; Volkov, V.; Vollhardt, A.; Voneki, B.; Vorobyev, A.; Vorobyev, V.; Voß, C.; de Vries, J. A.; Vázquez Sierra, C.; Waldi, R.; Wallace, C.; Wallace, R.; Walsh, J.; Wang, J.; Ward, D. R.; Wark, H. M.; Watson, N. K.; Websdale, D.; Weiden, A.; Whitehead, M.; Wicht, J.; Wilkinson, G.; Wilkinson, M.; Williams, M.; Williams, M. P.; Williams, M.; Williams, T.; Wilson, F. F.; Wimberley, J.; Winn, M.; Wishahi, J.; Wislicki, W.; Witek, M.; Wormser, G.; Wotton, S. A.; Wraight, K.; Wyllie, K.; Xie, Y.; Xu, Z.; Yang, Z.; Yang, Z.; Yao, Y.; Yin, H.; Yu, J.; Yuan, X.; Yushchenko, O.; Zarebski, K. A.; Zavertyaev, M.; Zhang, L.; Zhang, Y.; Zhelezov, A.; Zheng, Y.; Zhu, X.; Zhukov, V.; Zonneveld, J. B.; Zucchelli, S.; LHCb Collaboration

2018-01-01

The decay Z → b b bar is reconstructed in pp collision data, corresponding to 2 fb-1 of integrated luminosity, collected by the LHCb experiment at a centre-of-mass energy of √{ s } = 8 TeV. The product of the Z production cross-section and the Z → b b bar branching fraction is measured for candidates in the fiducial region defined by two particle-level b-quark jets with pseudorapidities in the range 2.2 < η < 4.2, with transverse momenta pT > 20 GeV and dijet invariant mass in the range 45

[The Use of FTIR Coupled with Partial Least Square for Quantitative Analysis of the Main Composition of Bamboo/Polypropylene Composites].

PubMed

Lao, Wan-li; He, Yu-chan; Li, Gai-yun; Zhou, Qun

2016-01-01

The biomass to plastic ratio in wood plastic composites (WPCs) greatly affects the physical and mechanical properties and price. Fast and accurate evaluation of the biomass to plastic ratio is important for the further development of WPCs. Quantitative analysis of the WPC main composition currently relies primarily on thermo-analytical methods. However, these methods have some inherent disadvantages, including time-consuming, high analytical errors and sophisticated, which severely limits the applications of these techniques. Therefore, in this study, Fourier Transform Infrared (FTIR) spectroscopy in combination with partial least square (PLS) has been used for rapid prediction of bamboo and polypropylene (PP) content in bamboo/PP composites. The bamboo powders were used as filler after being dried at 105 degrees C for 24 h. PP was used as matrix materials, and some chemical regents were used as additives. Then 42 WPC samples with different ratios of bamboo and PP were prepared by the methods of extrusion. FTIR spectral data of 42 WPC samples were collected by means of KBr pellets technique. The model for bamboo and PP content prediction was developed by PLS-2 and full cross validation. Results of internal cross validation showed that the first derivative spectra in the range of 1 800-800 cm(-1) corrected by standard normal variate (SNV) yielded the optimal model. For both bamboo and PP calibration, the coefficients of determination (R2) were 0.955. The standard errors of calibration (SEC) were 1.872 for bamboo content and 1.848 for PP content, respectively. For both bamboo and PP validation, the R2 values were 0.950. The standard errors of cross validation (SECV) were 1.927 for bamboo content and 1.950 for PP content, respectively. And the ratios of performance to deviation (RPD) were 4.45 for both biomass and PP examinations. The results of external validation showed that the relative prediction deviations for both biomass and PP contents were lower than ± 6%. FTIR combined with PLS can be used for rapid and accurate determination of bamboo and PP content in bamboo/PP composites.

Maternal and Cord Serum Cytokine Changes with Continuous and Intermittent Labor Epidural Analgesia: A Randomized Study

PubMed Central

Mantha, Venkat R.; Vallejo, Manuel C.; Ramesh, Vimala; Jones, Bobby L.; Ramanathan, Sivam

2012-01-01

Background. Maternal fever during labor epidural analgesia (LEA) may cause increased maternal and cord serum inflammatory cytokines. We report the effects of intermittent and continuous LEA on these cytokines. Methods. Ninety-two women were randomly assigned to continuous (CLEA) or intermittent (ILEA) groups, 46 in each. Maternal temperature was checked and blood drawn at epidural insertion (baseline) and four-hourly until 4 h postpartum (4 PP). Cord blood was drawn after placental delivery. Interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), granulocyte macrophage-colony stimulating factor (GM-CSF), and tumor necrosis factor-α (TNF-α) were measured and analyzed according to group randomization, and then combined and reanalyzed as febrile (temperature ≥38°C) or afebrile groups. Results. Significant intragroup changes from baseline were noted in some groups. Data are pg/mL, median (Q1/Q3). IL-6 rose at all time points in all groups. CLEA: baseline: 18.5 (12.5/31.1), 4 h: 80.0 (46.3/110.8), 8 h: 171.9 (145.3/234.3), and 4 PP: 81 (55.7/137.4). ILEA: baseline: 15.7 (10.2/27.1), 4 h: 68.2 (33.3/95.0), 8 h: 125.0 (86.3/195.0), and 4 PP: 70.2 (54.8/103.6). Febrile group: baseline: 21.6 (13.8/40.9), 4 h: 83.9 (47.5/120.8), 8 h: 186.7 (149.6/349.9), and 4 PP: 105.8 (65.7/158.8). Afebrile group: baseline: 10.9 (2.1/17.4), 4 h: 38.2 (15.0/68.2), 8 h: 93.8 (57.1/135.7), and 4 PP: 52.9 (25.1/78). IL-8 rose at all time points in CLEA: baseline: 2.68 (0.0/4.3), 4 h: 3.7 (0.0/6.5), 8 h: 6.0 (3.3/9.6), 4 PP: 5.6 (0.8/8.0), and afebrile group baseline: 2.5 (0.0/4.7), 4 h: 3.3 (0.0/6.2), 8 h: 5.3 (1.9/9.8), and 4 PP: 4.7 (0.0/7.6). It fell at 4 PP in febrile group: baseline: 4.1 (0.0/6.4), 4 h: 3.8 (0.0/6.5), 8 h: 5.2 (2.5/8.0), and 4 PP: 2.9 (0.0/4.0). GM-CSF increased at 8 h and decreased at 4 PP in ILEA baseline: 2.73 (0.0/7.2), 4 h: 2.73 (0.0/7.9), 8 h: 3.9 (2.7/11.5), and 4 PP: 2.0 (0.0/7.2). It increased at 4 h and 8 h and decreased at 4 PP in febrile group: baseline: 2.6 (0.0/4.2), 4 h: 3.2 (2.1/7.0), 8 h: 4.0 (3.2/12.3), and 4 PP: 2.4 (1.7/12.6). There were no intergroup cytokine changes in maternal or cord serum in CLEA versus ILEA or febrile versus afebrile groups. Conclusions. Some cytokines, especially IL-6, rise physiologically during labor epidural analgesia. PMID:22629160

Measurement of the ratio of inclusive cross sections $$\\sigma (p\\bar{p} \\rightarrow Z+2~b~\\text{jets}) / \\sigma (p\\bar{p} \\rightarrow Z+ \\text{2 jets})$$ in $$p\\bar{p}$$ collisions at $$\\sqrt s=1.96$$ TeV

DOE PAGES

Abazov, V. M.

2015-03-17

In this study, we measure the ratio of cross sections, σ(pp¯ → Z + 2 b jets)/σ(pp¯ → Z + 2 jets), for associated production of a Z boson with at least two jets with transverse momentum p jet T > 20 GeV and pseudorapidity |η jet| < 2.5. This measurement uses data corresponding to an integrated luminosity of 9.7 fb –1 collected by the D0 experiment in Run II of Fermilab’s Tevatron pp¯ Collider at a center-of-mass energy of 1.96 TeV. The measured integrated ratio of 0.0236 ± 0.0032(stat) ± 0.0035(syst) is in agreement with predictions from next-to-leading-order perturbativemore » QCD and the Monte Carlo event generators PYTHIA and ALPGEN.« less

Uranium hydrogeochemical and stream sediment reconnaissance of the Cortez NTMS Quadrangle, Colorado/Utah, including concentrations of forty-three additional elements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Warren, R.G.

1979-05-01

During the summers of 1976, 1977, and 1978, 598 water and 1657 sediment samples were collected from 1775 locations within the 19,600-km/sup 2/ area of the Cortez Quadrangle, Colorado and Utah. Water samples were collected from streams, springs, and wells; sediment samples were collected from stream channels (wet and dry) and from springs. Each water sample was analyzed for 13 elements, and each sediment sample was analyzed for 43 elements. Uranium concentrations in water samples range from below the detection limit of 0.02 to 241.47 ppB and have a median of 0.87 ppB and a mean of 3.80 ppB. Backgroundmore » uranium concentrations are 2 to 5 ppB in several nonmountainous regions but are much lower in mountainous areas, particularly in the northeastern portion of the quadrangle. Water samples containing high uranium concentrations (>20 ppB) generally are associated with high conductivities, high concentrations of other metallic elements, and geologic units, such as the Mancos shale, that are unfavorable for uranium mineralization. However, four ground-water samples exhibit high uranium concentrations without concomitant high conductivities or high concentrations of other metallic elements. Two of these samples were collected from sites in the Slick Rock U--V district, and two were collected in the Morrison formation in the southern portion of the quadrangle where large uranium deposits are not known. Water samples collected from the northwestern corner of the quadrangle uniformly exhibit background uranium values but generally contain high nickel concentrations. In this area, U--Cu (White Canyon-type) deposits are hosted primarily by the Shinarump member of the Chinle formation. Uranium concentrations in sediment samples range from 0.51 to 76.41 ppM and have a median of 2.76 ppM and a mean of 3.08 ppM. Background uranium and metallic element concentrations decrease to the southwest from the highest values in the northeastern portion of the quadrangle.« less

ABCG2 transporter inhibitor restores the sensitivity of triple negative breast cancer cells to aminolevulinic acid-mediated photodynamic therapy.

PubMed

Palasuberniam, Pratheeba; Yang, Xue; Kraus, Daniel; Jones, Patrick; Myers, Kenneth A; Chen, Bin

2015-08-18

Photosensitizer protoporphyrin IX (PpIX) fluorescence, intracellular localization and cell response to photodynamic therapy (PDT) were analyzed in MCF10A normal breast epithelial cells and a panel of human breast cancer cells including estrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER2) positive and triple negative breast cancer (TNBC) cells after treatment with PpIX precursor aminolevulinic acid (ALA). Although PpIX fluorescence was heterogeneous in different cells, TNBC cells showed significantly lower PpIX level than MCF10A and ER- or HER2-positive cells. PpIX fluorescence in TNBC cells also had much less mitochondrial localization than other cells. There was an inverse correlation between PpIX fluorescence and cell viability after PDT. Breast cancer cells with the highest PpIX fluorescence were the most sensitive to ALA-PDT and TNBC cells with the lowest PpIX level were resistant to PDT. Treatment of TNBC cells with ABCG2 transporter inhibitor Ko143 significantly increased ALA-PpIX fluorescence, enhanced PpIX mitochondrial accumulation and sensitized cancer cells to ALA-PDT. Ko143 treatment had little effect on PpIX production and ALA-PDT in normal and ER- or HER2-positive cells. These results demonstrate that enhanced ABCG2 activity renders TNBC cell resistance to ALA-PDT and inhibiting ABCG2 transporter is a promising approach for targeting TNBC with ALA-based modality.

Nutritional geometry of calcium and phosphorus nutrition in broiler chicks. Growth performance, skeletal health and intake arrays.

PubMed

Bradbury, E J; Wilkinson, S J; Cronin, G M; Thomson, P C; Bedford, M R; Cowieson, A J

2014-07-01

The interaction between calcium (Ca) and non-phytate phosphorus (nPP) in broiler nutrition and skeletal health is highly complex with many factors influencing their digestion, absorption and utilisation. The use of an investigative model such as the geometric framework allows a graphical approach to explore these complex interactions. A total of 600 Ross 308-day-old male broiler chicks were allocated to one of 15 dietary treatments with five replicates and eight birds per replicate. Dietary treatments were formulated to one of three total densities of total Ca+nPP; high (15 g/kg), medium (13.5 g/kg) and low (12 g/kg) and at each density there were five different ratios of Ca : nPP (4, 2.75, 2.1, 1.5 and 1.14 : 1). Weekly performance data was collected and at the end of the experiment birds were individually weighed and the right leg removed for tibia ash analysis. Skeletal health was assessed using the latency to lie (LTL) at day 27. At low Ca and high nPP as well as high Ca and low nPP diets, birds had reduced feed intake, BW gain, poorer feed efficiency and lower tibia ash, resulting in a significant interaction between dietary Ca and nPP (P<0.05). LTL times were negatively influenced by diets having either a broad ratio (high Ca, low nPP) or too narrow a ratio (low Ca, high nPP) indicating that shorter LTL times may be influenced by the ratio of Ca : nPP rather than absolute concentrations of either mineral. The calculated intake arrays show that broilers more closely regulate Ca intake than nPP intake. Broilers are willing to over consume nPP to defend a Ca intake target more so than they are willing to over consume Ca to defend an nPP target. Overall dietary nPP was more influential on performance metrics, however, from the data it may appear that birds prioritise Ca intake over nPP and broadly ate to meet this requirement. As broilers are more willing to eat to a Ca intake target rather than an nPP intake target, this emphasises the importance of formulating diets to a accurately balanced density of Ca : nPP considering the biological importance of both minerals.

Protein phosphatase 2A: a highly regulated family of serine/threonine phosphatases implicated in cell growth and signalling.

PubMed Central

Janssens, V; Goris, J

2001-01-01

Protein phosphatase 2A (PP2A) comprises a family of serine/threonine phosphatases, minimally containing a well conserved catalytic subunit, the activity of which is highly regulated. Regulation is accomplished mainly by members of a family of regulatory subunits, which determine the substrate specificity, (sub)cellular localization and catalytic activity of the PP2A holoenzymes. Moreover, the catalytic subunit is subject to two types of post-translational modification, phosphorylation and methylation, which are also thought to be important regulatory devices. The regulatory ability of PTPA (PTPase activator), originally identified as a protein stimulating the phosphotyrosine phosphatase activity of PP2A, will also be discussed, alongside the other regulatory inputs. The use of specific PP2A inhibitors and molecular genetics in yeast, Drosophila and mice has revealed roles for PP2A in cell cycle regulation, cell morphology and development. PP2A also plays a prominent role in the regulation of specific signal transduction cascades, as witnessed by its presence in a number of macromolecular signalling modules, where it is often found in association with other phosphatases and kinases. Additionally, PP2A interacts with a substantial number of other cellular and viral proteins, which are PP2A substrates, target PP2A to different subcellular compartments or affect enzyme activity. Finally, the de-regulation of PP2A in some specific pathologies will be touched upon. PMID:11171037

Antidiabetic Polypill Improves Central Pathology and Cognitive Impairment in a Mixed Model of Alzheimer's Disease and Type 2 Diabetes.

PubMed

Infante-Garcia, Carmen; Ramos-Rodriguez, Juan Jose; Hierro-Bujalance, Carmen; Ortegon, Esperanza; Pickett, Eleanor; Jackson, Rosemary; Hernandez-Pacho, Fernando; Spires-Jones, Tara; Garcia-Alloza, Monica

2018-07-01

Type 2 diabetes (T2D) is an important risk factor to suffer dementia, being Alzheimer's disease (AD) as the most common form. Both AD and T2D are closely related to aging and with a growing elderly population it might be of relevance to explore new therapeutic approaches that may slow or prevent central complications associated with metabolic disorders. Therefore, we propose the use of the antidiabetic polypill (PP), a pharmacological cocktail, commonly used by T2D patients that include metformin, aspirin, simvastatin, and an angiotensin-converting enzyme inhibitor. In order to test the effects of PP at the central level, we have long-term treated a new mixed model of AD-T2D, the APP/PS1xdb/db mouse. We have analyzed AD pathological features and the underlying specific characteristics that relate AD and T2D. As expected, metabolic alterations were ameliorated after PP treatment in diabetic mice, supporting a role for PP in maintaining pancreatic activity. At central level, PP reduced T2D-associated brain atrophy, showing both neuronal and synaptic preservation. Tau and amyloid pathologies were also reduced after PP treatment. Furthermore, we observed a reduction of spontaneous central bleeding and inflammation after PP treatment in diabetic mice. As consequence, learning and memory processes were improved after PP treatment in AD, T2D, and AD-T2D mice. Our data provide the basis to further analyze the role of PP, as an alternative or adjuvant, to slow down or delay the central complications associated with T2D and AD.

Pharmacological Activation of Protein Phosphatase 2 A (PP2A): A Novel Strategy to Fight Against Human Malignancies?

PubMed

Carratù, Maria Rosaria; Signorile, Anna; De Rasmo, Domenico; Reale, Antonia; Vacca, Angelo

2016-01-01

The serine-threonine protein phosphatase 2A (PP2A) regulates multiple cell signaling cascades and its inactivation by viral oncoproteins, mutation of specific structural subunits or upregulation of the cellular endogenous inhibitors may contribute to malignant transformation by regulating specific phosphorylation events. Pharmacological modulation of PP2A activity is becoming an attractive strategy for cancer treatment. Some compounds targeting PP2A are able to induce PP2A reactivation and subsequent cell death in several types of cancer. We undertook a search of bibliographic databases for peer-reviewed articles focusing on the main item of the review. We selected articles published in indexed journals. The quality of retrieved papers was appraised using the standard bibliometric indicators. One hundred and fourteen papers were included in the review. Twenty-seven papers gave an overview of structure and physiological role of PP2A. Twenty-five papers outlined the role of PP2A in tumor suppression. Forty papers analyzed the mechanism involved in PP2A reactivation by synthetic compounds, and twenty-two papers outlined the capability of natural compounds of restoring PP2A activity and how this could be beneficial. Findings analyzed in this review underline the central role of PP2A as a regulator of cell growth and survival, hence its function as tumor suppressor. The discovery that some compounds, either synthetic or natural, are capable of reactivating PP2A opens up new perspectives for future strategies to fully exploit therapeutic potential in human cancer. Thus, this review could also be of particular interest to pharmaceutical or biotechnology companies for drug design and targeted delivery.

Crystal structures and mutagenesis of PPP-family ser/thr protein phosphatases elucidate the selectivity of cantharidin and novel norcantharidin-based inhibitors of PP5C.

PubMed

Chattopadhyay, Debasish; Swingle, Mark R; Salter, Edward A; Wood, Eric; D'Arcy, Brandon; Zivanov, Catherine; Abney, Kevin; Musiyenko, Alla; Rusin, Scott F; Kettenbach, Arminja; Yet, Larry; Schroeder, Chad E; Golden, Jennifer E; Dunham, Wade H; Gingras, Anne-Claude; Banerjee, Surajit; Forbes, David; Wierzbicki, Andrzej; Honkanen, Richard E

2016-06-01

Cantharidin is a natural toxin and an active constituent in a traditional Chinese medicine used to treat tumors. Cantharidin acts as a semi-selective inhibitor of PPP-family ser/thr protein phosphatases. Despite sharing a common catalytic mechanism and marked structural similarity with PP1C, PP2AC and PP5C, human PP4C was found to be insensitive to the inhibitory activity of cantharidin. To explore the molecular basis for this selectivity, we synthesized and tested novel C5/C6-derivatives designed from quantum-based modeling of the interactions revealed in the co-crystal structures of PP5C in complex with cantharidin. Structure-activity relationship studies and analysis of high-resolution (1.25Å) PP5C-inhibitor co-crystal structures reveal close contacts between the inhibitor bridgehead oxygen and both a catalytic metal ion and a non-catalytic phenylalanine residue, the latter of which is substituted by tryptophan in PP4C. Quantum chemistry calculations predicted that steric clashes with the bulkier tryptophan side chain in PP4C would force all cantharidin-based inhibitors into an unfavorable binding mode, disrupting the strong coordination of active site metal ions observed in the PP5C co-crystal structures, thereby rendering PP4C insensitive to the inhibitors. This prediction was confirmed by inhibition studies employing native human PP4C. Mutation of PP5C (F446W) and PP1C (F257W), to mimic the PP4C active site, resulted in markedly suppressed sensitivity to cantharidin. These observations provide insight into the structural basis for the natural selectivity of cantharidin and provide an avenue for PP4C deselection. The novel crystal structures also provide insight into interactions that provide increased selectivity of the C5/C6 modifications for PP5C versus other PPP-family phosphatases. Copyright © 2016 Elsevier Inc. All rights reserved.

The C. elegans RSA complex localizes protein phosphatase 2A to centrosomes and regulates mitotic spindle assembly.

PubMed

Schlaitz, Anne-Lore; Srayko, Martin; Dammermann, Alexander; Quintin, Sophie; Wielsch, Natalie; MacLeod, Ian; de Robillard, Quentin; Zinke, Andrea; Yates, John R; Müller-Reichert, Thomas; Shevchenko, Andrei; Oegema, Karen; Hyman, Anthony A

2007-01-12

Microtubule behavior changes during the cell cycle and during spindle assembly. However, it remains unclear how these changes are regulated and coordinated. We describe a complex that targets the Protein Phosphatase 2A holoenzyme (PP2A) to centrosomes in C. elegans embryos. This complex includes Regulator of Spindle Assembly 1 (RSA-1), a targeting subunit for PP2A, and RSA-2, a protein that binds and recruits RSA-1 to centrosomes. In contrast to the multiple functions of the PP2A catalytic subunit, RSA-1 and RSA-2 are specifically required for microtubule outgrowth from centrosomes and for spindle assembly. The centrosomally localized RSA-PP2A complex mediates these functions in part by regulating two critical mitotic effectors: the microtubule destabilizer KLP-7 and the C. elegans regulator of spindle assembly TPXL-1. By regulating a subset of PP2A functions at the centrosome, the RSA complex could therefore provide a means of coordinating microtubule outgrowth from centrosomes and kinetochore microtubule stability during mitotic spindle assembly.

Effect of blend ratio of PP/kapok blend nonwoven fabrics on oil sorption capacity.

PubMed

Lee, Young-Hee; Kim, Ji-Soo; Kim, Do-Hyung; Shin, Min-Seung; Jung, Young-Jin; Lee, Dong-Jin; Kim, Han-Do

2013-01-01

More research and development on novel oil sorbent materials is needed to protect the environmental pollution. New nonwoven fabrics (pads) of polypropylene (PP)/kapok blends (blend ratio: 100/0, 75/25, 50/50, 25/75 and 10/90) were prepared by needle punching process at a fixed (optimized) condition (punch density: 50 punches/cm2 and depth: 4mm). This study focused on the effect of blend ratio of PP/kapok nonwoven fabrics on oil sorption capacities to find the best blend ratio having the highest synergy effect. The PP/kapok blend (50/50) sample has the lowest bulk density and showed the best oil absorption capacity. The oil sorption capacity of PP/kapok blend (50/50) nonwoven fabric for kerosene/soybean oil [21.09/27.01 (g oil/g sorbent)] was 1.5-2 times higher than those of commercial PP pad oil sorbents. The highest synergy effect of PP/kapok blend (50/50) was ascribed to the lowest bulk density of PP/kapok blend (50/50), which might be due to the highest morphologically incompatibility between PP fibre and kapok. These results suggest that the PP/kapok blend (50/50) having the highest synergy effect has a high potential as a new high-performance oil sorbent material.

Ketamine, a Clinically Used Anesthetic, Inhibits Vascular Smooth Muscle Cell Proliferation via PP2A-Activated PI3K/Akt/ERK Inhibition

PubMed Central

Chang, Yi; Li, Jiun-Yi; Jayakumar, Thanasekaran; Hung, Shou-Huang; Lee, Wei-Cheng; Manubolu, Manjunath; Sheu, Joen-Rong; Hsu, Ming-Jen

2017-01-01

Abnormal proliferation of vascular smooth muscle cells (VSMCs) gives rise to major pathological processes involved in the development of cardiovascular diseases. The use of anti-proliferative agents for VSMCs offers potential for the treatment of vascular disorders. Intravenous anesthetics are firmly established to have direct effects on VSMCs, resulting in modulation of blood pressure. Ketamine has been used for many years in the intensive care unit (ICU) for sedation, and has recently been considered for adjunctive therapy. In the present study, we investigated the effects of ketamine on platelet-derived growth factor BB (PDGF-BB)-induced VSMC proliferation and the associated mechanism. Ketamine concentration-dependently inhibited PDGF-BB-induced VSMC proliferation without cytotoxicity, and phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated protein kinase (ERK) inhibitors, LY294002 and PD98059, respectively, have similar inhibitory effects. Ketamine was shown to attenuate PI3K, Akt, and ERK1/2 phosphorylation induced by PDGF-BB. Okadaic acid, a selective protein phosphatase 2A (PP2A) inhibitor, significantly reversed ketamine-mediated PDGF-BB-induced PI3K, Akt, and ERK1/2 phosphorylation; a transfected protein phosphatse 2a (pp2a) siRNA reversed Akt and ERK1/2 phosphorylation; and 3-O-Methyl-sphingomyeline (3-OME), an inhibitor of sphingomyelinase, also significantly reversed ERK1/2 phosphorylation. Moreover, ketamine alone significantly inhibited tyrosine phosphorylation and demethylation of PP2A in a concentration-dependent manner. In addition, the pp2a siRNA potently reversed the ketamine-activated catalytic subunit (PP2A-C) of PP2A. These results provide evidence of an anti-proliferating effect of ketamine in VSMCs, showing activation of PP2A blocks PI3K, Akt, and ERK phosphorylation that subsequently inhibits the proliferation of VSMCs. Thus, ketamine may be considered a potential effective therapeutic agent for reducing atherosclerotic process by blocking the proliferation of VSMCs. PMID:29186909

Ketamine, a Clinically Used Anesthetic, Inhibits Vascular Smooth Muscle Cell Proliferation via PP2A-Activated PI3K/Akt/ERK Inhibition.

PubMed

Chang, Yi; Li, Jiun-Yi; Jayakumar, Thanasekaran; Hung, Shou-Huang; Lee, Wei-Cheng; Manubolu, Manjunath; Sheu, Joen-Rong; Hsu, Ming-Jen

2017-11-27

Abnormal proliferation of vascular smooth muscle cells (VSMCs) gives rise to major pathological processes involved in the development of cardiovascular diseases. The use of anti-proliferative agents for VSMCs offers potential for the treatment of vascular disorders. Intravenous anesthetics are firmly established to have direct effects on VSMCs, resulting in modulation of blood pressure. Ketamine has been used for many years in the intensive care unit (ICU) for sedation, and has recently been considered for adjunctive therapy. In the present study, we investigated the effects of ketamine on platelet-derived growth factor BB (PDGF-BB)-induced VSMC proliferation and the associated mechanism. Ketamine concentration-dependently inhibited PDGF-BB-induced VSMC proliferation without cytotoxicity, and phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated protein kinase (ERK) inhibitors, LY294002 and PD98059, respectively, have similar inhibitory effects. Ketamine was shown to attenuate PI3K, Akt, and ERK1/2 phosphorylation induced by PDGF-BB. Okadaic acid, a selective protein phosphatase 2A (PP2A) inhibitor, significantly reversed ketamine-mediated PDGF-BB-induced PI3K, Akt, and ERK1/2 phosphorylation; a transfected protein phosphatse 2a ( pp2a ) siRNA reversed Akt and ERK1/2 phosphorylation; and 3-O-Methyl-sphingomyeline (3-OME), an inhibitor of sphingomyelinase, also significantly reversed ERK1/2 phosphorylation. Moreover, ketamine alone significantly inhibited tyrosine phosphorylation and demethylation of PP2A in a concentration-dependent manner. In addition, the pp2a siRNA potently reversed the ketamine-activated catalytic subunit (PP2A-C) of PP2A. These results provide evidence of an anti-proliferating effect of ketamine in VSMCs, showing activation of PP2A blocks PI3K, Akt, and ERK phosphorylation that subsequently inhibits the proliferation of VSMCs. Thus, ketamine may be considered a potential effective therapeutic agent for reducing atherosclerotic process by blocking the proliferation of VSMCs.

Tripodal polyphosphine ligands as inductors of chelate ring-opening processes in mononuclear palladium(II) and platinum(II) compounds. The X-ray crystal structure of two derivatives containing dangling phosphorus.

PubMed

Fernández-Anca, Damián; García-Seijo, M Inés; García-Fernández, M Esther

2010-03-07

The reaction of NP(3) (tris[2-(diphenylphosphino)ethyl]amine and PP(3) (tris[2-(diphenylphosphino)ethyl]phosphine) with the five-coordinate complexes [PdCl(NP(3))]Cl (1) and [MX(PP(3))]X [M = Pd: X = Cl(2), Br(3), I(4); M = Pt: X = Cl(5), Br(6), I(7)], respectively, followed by (31)P{(1)H}NMR when X = Cl, led to the formation of unprecedented four-coordinate halides in a 1 : 2 metal to ligand ratio, [M(AP(3))(2)]X(2) [A = N, M = Pd: X = Cl(8); A = P, M = Pd: X = Cl(9), Br(10), I(11); A = P, M = Pt: X = Cl(12), Br(13), I (14)], containing reactive dangling phosphorus. Given the non characterised precursors [M(ONO(2))(PP(3))](NO(3))], the interaction between the heteronuclear species [MAg(NO(3))(3)(PP(3))] [M = Pd(15), Pt(16)] and PP(3) was explored. It was found that the addition of 1 equivalent of phosphine afforded [MAg(NO(3))(PP(3))(2)](NO(3))(2) [M = Pd(15*), Pt(16*)] containing Ag(I) bound to two dangling phosphorus while the reaction with 2 equivalents led to the complexes [M(PP(3))(2)](NO(3))(2) [M = Pd (17), Pt (18)] in coexistence with [Ag(2)(mu-PP(3))(2)](NO(3))(2). The fate of Ag(I) on the reaction of the mixed metal compounds with excess PP(3) consisted of preventing dissociation, observed in solution for halides, and acting as an assistant for crystallization. Colourless single crystals of 18 and 10, studied by X-ray diffraction, were afforded by reaction of 16 with 4 equivalents of PP(3) and from solutions of 10 in chloroform coexisting with red crystals of 3, respectively. The structures revealed the presence of dications [M(PP(3))(2)](2+) that show two five-membered chelate rings to M(II) in a square-planar arrangement and four uncoordinated phosphine arms with the counter anions being symmetrically placed at 4.431 (Br(-)) and 13.823 (NO(3)(-)) A from M(II) above and below its coordination, MP(4), plane. Complexes 9 and 12 were shown to undergo an interesting reactivity in solution versus group 11 monocations. The reactions consisted of conversions of the two five-membered chelate rings to M into three (structure I) or two (structure II) fused five-membered chelate rings, formation of species where Pt(II) retained its square-planar environment with the two dangling phosphine arms of each PP(3) bound to Cu(I) or Ag(I) (structure III) and complexes bearing distorted square-planar (P(2)MCl(2)) and presumably tetrahedral (AuP(4)+ P(2)AuCl(2)) arrangements (structure IV). The processes with Ag(I) salts also gave mixtures of I+III (chloride and nitrate) or II+III (nitrate).

Mechanical properties of PP/PA blends in addition with PP-g-MAH with different PP molecular weight and MAH content

NASA Astrophysics Data System (ADS)

Tokumitsu, Katuhisa; Nakajima, Yuki; Aoki, Kenji

2016-03-01

The mechanical properties and morphological changes of PP/PA6/PP-g-MAH blends were investigated. In particular, various kinds of PP-g-MAH, which have a series of different Mw of PP and MAH content, were investigated. From the tensile test results of PP/PA6 blends, although the elongation at break and yield stress can be improved by adding PP-g-MAH, modulus slightly decreased. In particular, elongation at break of PP/PA in addition with PP-g-MAH increased twentyfold from 27.0% (without PP-g-MAH) to 570%. On the basis of Charpy impact test results, the impact strength can also be improved by adding PP-g-MAH. From SEM observation, it was found that the diameter of the dispersed PA6 phase in PP matrix was getting much smaller with PP-g-MAH content. From the TEM observation, the boundary of the PA phase in PP/PA blends without PP-g-MAH compatibilizer can be observed clearly, but it becomes hard to see the boundary part of the PA phase in PP/PA blend with compatibilizer. Furthermore, when comparing the inside of the PA phase, small amount of PP phase can be observed in the PA phase of PP/PA blend with compatibilizer. Here, we defined a parameter, Comprehensive Mechanical Property Factor (CMPF), which can be calculated by multiple each mechanical property (elongation at break, yield stress, modulus and impact strength) against each maximum value, and it was found that CMPF has a good correlation with the diameter of PA6 phase. In conclusion, an optimum mechanical property of PP/PA6 can be obtained by using PP-g-MAH with Mw around 35,000 ˜ 50,000 g mol-1 and MAH content around 2.0 ˜ 3.5 %.

Molecular Mimicry Regulates ABA Signaling by SnRK2 Kinases and PP2C Phosphatases

PubMed Central

Soon, Fen-Fen; Ng, Ley-Moy; Zhou, X. Edward; West, Graham M.; Kovach, Amanda; Tan, M. H. Eileen; Suino-Powell, Kelly M.; He, Yuanzheng; Xu, Yong; Chalmers, Michael J.; Brunzelle, Joseph S.; Zhang, Huiming; Yang, Huaiyu; Jiang, Hualiang; Li, Jun; Yong, Eu-Leong; Cutler, Sean; Zhu, Jian-Kang; Griffin, Patrick R.; Melcher, Karsten; Xu, H. Eric

2013-01-01

Abscisic acid (ABA) is an essential hormone for plants to survive environmental stresses. At the center of the ABA signaling network is a subfamily of type 2C protein phosphatases (PP2Cs), which form exclusive interactions with ABA receptors and subfamily 2 Snfl-related kinase (SnRK2s). Here, we report a SnRK2-PP2C complex structure, which reveals marked similarity in PP2C recognition by SnRK2 and ABA receptors. In the complex, the kinase activation loop docks into the active site of PP2C, while the conserved ABA-sensing tryptophan of PP2C inserts into the kinase catalytic cleft, thus mimicking receptor-PP2C interactions. These structural results provide a simple mechanism that directly couples ABA binding to SnRK2 kinase activation and highlight a new paradigm of kinase-phosphatase regulation through mutual packing of their catalytic sites. PMID:22116026

Molecular Mimicry Regulates ABA Signaling by SnRK2 Kinases and PP2C Phosphatases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Soon, Fen-Fen; Ng, Ley-Moy; Zhou, X. Edward

Abscisic acid (ABA) is an essential hormone for plants to survive environmental stresses. At the center of the ABA signaling network is a subfamily of type 2C protein phosphatases (PP2Cs), which form exclusive interactions with ABA receptors and subfamily 2 Snfl-related kinase (SnRK2s). Here, we report a SnRK2-PP2C complex structure, which reveals marked similarity in PP2C recognition by SnRK2 and ABA receptors. In the complex, the kinase activation loop docks into the active site of PP2C, while the conserved ABA-sensing tryptophan of PP2C inserts into the kinase catalytic cleft, thus mimicking receptor-PP2C interactions. These structural results provide a simple mechanismmore » that directly couples ABA binding to SnRK2 kinase activation and highlight a new paradigm of kinase-phosphatase regulation through mutual packing of their catalytic sites.« less

Catalytic Subunit 1 of Protein Phosphatase 2A Is a Subunit of the STRIPAK Complex and Governs Fungal Sexual Development.

PubMed

Beier, Anna; Teichert, Ines; Krisp, Christoph; Wolters, Dirk A; Kück, Ulrich

2016-06-21

The generation of complex three-dimensional structures is a key developmental step for most eukaryotic organisms. The details of the molecular machinery controlling this step remain to be determined. An excellent model system to study this general process is the generation of three-dimensional fruiting bodies in filamentous fungi like Sordaria macrospora Fruiting body development is controlled by subunits of the highly conserved striatin-interacting phosphatase and kinase (STRIPAK) complex, which has been described in organisms ranging from yeasts to humans. The highly conserved heterotrimeric protein phosphatase PP2A is a subunit of STRIPAK. Here, catalytic subunit 1 of PP2A was functionally characterized. The Δpp2Ac1 strain is sterile, unable to undergo hyphal fusion, and devoid of ascogonial septation. Further, PP2Ac1, together with STRIPAK subunit PRO22, governs vegetative and stress-related growth. We revealed in vitro catalytic activity of wild-type PP2Ac1, and our in vivo analysis showed that inactive PP2Ac1 blocks the complementation of the sterile deletion strain. Tandem affinity purification, followed by mass spectrometry and yeast two-hybrid analysis, verified that PP2Ac1 is a subunit of STRIPAK. Further, these data indicate links between the STRIPAK complex and other developmental signaling pathways, implying the presence of a large interconnected signaling network that controls eukaryotic developmental processes. The insights gained in our study can be transferred to higher eukaryotes and will be important for understanding eukaryotic cellular development in general. The striatin-interacting phosphatase and kinase (STRIPAK) complex is highly conserved from yeasts to humans and is an important regulator of numerous eukaryotic developmental processes, such as cellular signaling and cell development. Although functional insights into the STRIPAK complex are accumulating, the detailed molecular mechanisms of single subunits are only partially understood. The first fungal STRIPAK was described in Sordaria macrospora, which is a well-established model organism used to study the formation of fungal fruiting bodies, three-dimensional organ-like structures. We analyzed STRIPAK subunit PP2Ac1, catalytic subunit 1 of protein phosphatase PP2A, to study the importance of the catalytic activity of this protein during sexual development. The results of our yeast two-hybrid analysis and tandem affinity purification, followed by mass spectrometry, indicate that PP2Ac1 activity connects STRIPAK with other signaling pathways and thus forms a large interconnected signaling network. Copyright © 2016 Beier et al.

Pin1At regulates PIN1 polar localization and root gravitropism.

PubMed

Xi, Wanyan; Gong, Ximing; Yang, Qiaoyun; Yu, Hao; Liou, Yih-Cherng

2016-01-21

Root gravitropism allows plants to establish root systems and its regulation depends on polar auxin transport mediated by PIN-FORMED (PIN) auxin transporters. PINOID (PID) and PROTEIN PHOSPHATASE 2A (PP2A) act antagonistically on reversible phosphorylation of PINs. This regulates polar PIN distribution and auxin transport. Here we show that a peptidyl-prolyl cis/trans isomerase Pin1At regulates root gravitropism. Downregulation of Pin1At suppresses root agravitropic phenotypes of pp2aa and 35S:PID, while overexpression of Pin1At affects root gravitropic responses and enhances the pp2aa agravitropic phenotype. Pin1At also affects auxin transport and polar localization of PIN1 in stele cells, which is mediated by PID and PP2A. Furthermore, Pin1At catalyses the conformational change of the phosphorylated Ser/Thr-Pro motifs of PIN1. Thus, Pin1At mediates the conformational dynamics of PIN1 and affects PID- and PP2A-mediated regulation of PIN1 polar localization, which correlates with the regulation of root gravitropism.

Pin1At regulates PIN1 polar localization and root gravitropism

PubMed Central

Xi, Wanyan; Gong, Ximing; Yang, Qiaoyun; Yu, Hao; Liou, Yih-Cherng

2016-01-01

Root gravitropism allows plants to establish root systems and its regulation depends on polar auxin transport mediated by PIN-FORMED (PIN) auxin transporters. PINOID (PID) and PROTEIN PHOSPHATASE 2A (PP2A) act antagonistically on reversible phosphorylation of PINs. This regulates polar PIN distribution and auxin transport. Here we show that a peptidyl-prolyl cis/trans isomerase Pin1At regulates root gravitropism. Downregulation of Pin1At suppresses root agravitropic phenotypes of pp2aa and 35S:PID, while overexpression of Pin1At affects root gravitropic responses and enhances the pp2aa agravitropic phenotype. Pin1At also affects auxin transport and polar localization of PIN1 in stele cells, which is mediated by PID and PP2A. Furthermore, Pin1At catalyses the conformational change of the phosphorylated Ser/Thr-Pro motifs of PIN1. Thus, Pin1At mediates the conformational dynamics of PIN1 and affects PID- and PP2A-mediated regulation of PIN1 polar localization, which correlates with the regulation of root gravitropism. PMID:26791759

Lysyl oxidase propeptide inhibits smooth muscle cell signaling and proliferation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hurtado, Paola A.; Vora, Siddharth; Sume, Siddika Selva

2008-02-01

Lysyl oxidase is required for the normal biosynthesis and maturation of collagen and elastin. It is expressed by vascular smooth muscle cells, and its increased expression has been previously found in atherosclerosis and in models of balloon angioplasty. The lysyl oxidase propeptide (LOX-PP) has more recently been found to have biological activity as a tumor suppressor, and it inhibits Erk1/2 Map kinase activation. We reasoned that LOX-PP may have functions in normal non-transformed cells. We, therefore, investigated its effects on smooth muscle cells, focusing on important biological processes mediated by Erk1/2-dependent signaling pathways including proliferation and matrix metalloproteinase-9 (MMP-9) expression.more » In addition, we investigated whether evidence for accumulation of LOX-PP could be found in vivo in a femoral artery injury model. Recombinant LOX-PP was expressed and purified, and was found to inhibit primary rat aorta smooth muscle cell proliferation and DNA synthesis by more than 50%. TNF-{alpha}-stimulated MMP-9 expression and Erk1/2 activation were both significantly inhibited by LOX-PP. Immunohistochemistry studies carried out with affinity purified anti-LOX-PP antibody showed that LOX-PP epitopes were expressed at elevated levels in vascular lesions of injured arteries. These novel data suggest that LOX-PP may provide a feedback control mechanism that serves to inhibit properties associated with the development of vascular pathology.« less

Toxicology of oxides of nitrogen. I. Toxic concentrations

DOE Office of Scientific and Technical Information (OSTI.GOV)

La Towsky, L.W.; MacQuiddy, E.L.; Tollman, J.P.

1941-01-01

One hundred twelve rabbits, cats, guinea pigs, rats, and mice were exposed to 30 to 1000 ppM NO/sub 2/. Average time to produce death was: 30 ppM - none in 3 hr, 100 ppM - 318 min, 150 ppM - 90 min, 400 ppM - 58 min, 600 ppM - 32 min, 800 ppM - 29 min, 1000 ppM - 19 min. Rats and mice were more sensitive, sometimes exhibiting delayed effects (e.g., 2 to 3 hr at 55 ppM). Cats were most sensitive in that they thrash excitedly, thus breathing more. Methemoglobin was frequently seen in blood during exposure.more » Death was from edema (most common), asphyxia, or pneumonitis (secondary).« less

PP13, Maternal ABO Blood Groups and the Risk Assessment of Pregnancy Complications

PubMed Central

Than, Nandor Gabor; Romero, Roberto; Meiri, Hamutal; Erez, Offer; Xu, Yi; Tarquini, Federica; Barna, Laszlo; Szilagyi, Andras; Ackerman, Ron; Sammar, Marei; Fule, Tibor; Karaszi, Katalin; Kovalszky, Ilona; Dong, Zhong; Kim, Chong Jai; Zavodszky, Peter; Papp, Zoltan; Gonen, Ron

2011-01-01

Background Placental Protein 13 (PP13), an early biomarker of preeclampsia, is a placenta-specific galectin that binds beta-galactosides, building-blocks of ABO blood-group antigens, possibly affecting its bioavailability in blood. Methods and Findings We studied PP13-binding to erythrocytes, maternal blood-group effect on serum PP13 and its performance as a predictor of preeclampsia and intrauterine growth restriction (IUGR). Datasets of maternal serum PP13 in Caucasian (n = 1078) and Hispanic (n = 242) women were analyzed according to blood groups. In vivo, in vitro and in silico PP13-binding to ABO blood-group antigens and erythrocytes were studied by PP13-immunostainings of placental tissue-microarrays, flow-cytometry of erythrocyte-bound PP13, and model-building of PP13 - blood-group H antigen complex, respectively. Women with blood group AB had the lowest serum PP13 in the first trimester, while those with blood group B had the highest PP13 throughout pregnancy. In accordance, PP13-binding was the strongest to blood-group AB erythrocytes and weakest to blood-group B erythrocytes. PP13-staining of maternal and fetal erythrocytes was revealed, and a plausible molecular model of PP13 complexed with blood-group H antigen was built. Adjustment of PP13 MoMs to maternal ABO blood group improved the prediction accuracy of first trimester maternal serum PP13 MoMs for preeclampsia and IUGR. Conclusions ABO blood group can alter PP13-bioavailability in blood, and it may also be a key determinant for other lectins' bioavailability in the circulation. The adjustment of PP13 MoMs to ABO blood group improves the predictive accuracy of this test. PMID:21799738

New pentacoordinated rhodium species as unexpected products during the in situ generation of dimeric diphosphine-rhodium neutral catalysts.

PubMed

Meissner, Antje; König, Anja; Drexler, Hans-Joachim; Thede, Richard; Baumann, Wolfgang; Heller, Detlef

2014-11-03

Dimeric rhodium complexes of the type [Rh(PP)(μ2 -Cl)]2 (PP=diphosphine) are often used as precatalysts and are generated "in situ" from the corresponding diolefin complexes by exchange of the diene with the desired diphosphine. Herein, we report that the "in situ" procedure also leads to unexpected monomeric pentacoordinated neutral complexes of the type [RhCl(PP)(diolefin)], for the first time herein characterized by NMR spectroscopy and X-ray crystallography for the ligands 1,4-bis(diphenylphosphino)propane (DPPP), 1,4-bis(diphenylphosphino)butane (DPPB), and 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP). The pentacoordinated complexes are in equilibrium with the dimeric target compound [Rh(PP)(μ2 -Cl)]2 . The equilibrium is influenced by the rhodium-diolefin precursor, the solvent and the temperature. Based on the results of NMR and UV/Vis spectroscopic analysis (kinetics) it could be shown that the pentacoordinated complex [RhCl(PP)(diolefin)] may arise both from the "in situ"-generated neutral complex [Rh(PP)(μ2 -Cl)] by reaction with the free diolefin and, more surprisingly, directly from [Rh(diolefin)(μ2 -Cl)]2 and the diphosphine. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Z Xu; C Chen; Y Wang

Combined effects of graphene nanosheets (GNSs) and shear flow on the crystallization behavior of isotactic polypropylene (iPP) were investigated by in-situ synchrotron wide-angle X-ray diffraction (WAXD) and small-angle X-ray scattering (SAXS) techniques. For crystallization under quiescent condition (at 145 C), the half-crystallization time (t{sub 1/2}) of nanocomposites containing 0.05 and 0.1 wt % GNSs was reduced to at least 50% compared to that of neat iPP, indicating the high nucleation ability of GNSs. The crystallization rate of iPP was directly proportional to the GNS content. Under a relatively weak shear flow (at a rate of 20 s{sup -1} for 5more » s duration) and a low degree of supercooling, the neat iPP exhibited an isotropic structure due to the relaxation of row nuclei. However, visible antisotropic crystals appeared in sheared iPP/GNSs nanocomposites, indicating that GNSs induced a network structure hindering the mobility of iPP chains and allowing the survival of oriented row nuclei for a long period of time. The presence of GNSs clearly enhanced the effects of shear-induced nucleation as well as orientation of iPP crystals. Two kinds of nucleating origins coexisted in the sheared nanocomposite melt: heterogeneous nucleating sites initiated by GNSs and homogeneous nucleating sites (row nuclei) induced by shear. The difference of t{sub 1/2} of nanocomposites with and without shear was significantly larger than that of neat iPP. The presence of GNSs and shear flow exhibited a synergistic interaction on promoting crystallization kinetics of iPP, although the effect of GNS concentration was not apparent. From WAXD results of isothermal and nonisothermal crystallization of sheared iPP, it was found that the appearance of {beta}-crystals depended on the preservation of row nuclei, where the {alpha}-crystals were predominant in the iPP/GNSs nanocomposites, indicating that GNSs could directly induce {alpha}-crystals of iPP.« less

Direct laser writing of synthetic poly(amino acid) hydrogels and poly(ethylene glycol) diacrylates by two-photon polymerization.

PubMed

Käpylä, Elli; Sedlačík, Tomáš; Aydogan, Dogu Baran; Viitanen, Jouko; Rypáček, František; Kellomäki, Minna

2014-10-01

The additive manufacturing technique of direct laser writing by two-photon polymerization (2PP-DLW) enables the fabrication of three-dimensional microstructures with superior accuracy and flexibility. When combined with biomimetic hydrogel materials, 2PP-DLW can be used to recreate the microarchitectures of the extracellular matrix. However, there are currently only a limited number of hydrogels applicable for 2PP-DLW. In order to widen the selection of synthetic biodegradable hydrogels, in this work we studied the 2PP-DLW of methacryloylated and acryloylated poly(α-amino acid)s (poly(AA)s). The performance of these materials was compared to widely used poly(ethylene glycol) diacrylates (PEGdas) in terms of polymerization and damage thresholds, voxel size, line width, post-polymerization swelling and deformation. We found that both methacryloylated and acryloylated poly(AA) hydrogels are suitable to 2PP-DLW with a wider processing window than PEGdas. The poly(AA) with the highest degree of acryloylation showed the greatest potential for 3D microfabrication. Copyright © 2014 Elsevier B.V. All rights reserved.

Overexpression of the protein phosphatase 2A regulatory subunit a gene ZmPP2AA1 improves low phosphate tolerance by remodeling the root system architecture of maize

PubMed Central

Wang, Jiemin; Pei, Laming; Jin, Zhe; Zhang, Kewei; Zhang, Juren

2017-01-01

Phosphate (Pi) limitation is a constraint for plant growth and development in many natural and agricultural ecosystems. In this study, a gene encoding Zea mays L. protein phosphatase 2A regulatory subunit A, designated ZmPP2AA1, was induced in roots by low Pi availability. The function of the ZmPP2AA1 gene in maize was analyzed using overexpression and RNA interference. ZmPP2AA1 modulated root gravitropism, negatively regulated primary root (PR) growth, and stimulated the development of lateral roots (LRs). A detailed characterization of the root system architecture (RSA) in response to different Pi concentrations with or without indole-3-acetic acid and 1-N-naphthylphthalamic acid revealed that auxin was involved in the RSA response to low Pi availability. Overexpression of ZmPP2AA1 enhanced tolerance to Pi starvation in transgenic maize in hydroponic and soil pot experiments. An increased dry weight (DW), root-to-shoot ratio, and total P content and concentration, along with a delayed and reduced accumulation of anthocyanin in overexpressing transgenic maize plants coincided with their highly branched root system and increased Pi uptake capability under low Pi conditions. Inflorescence development of the ZmPP2AA1 overexpressing line was less affected by low Pi stress, resulting in higher grain yield per plant under Pi deprivation. These data reveal the biological function of ZmPP2AA1, provide insights into a linkage between auxin and low Pi responses, and drive new strategies for the efficient utilization of Pi by maize. PMID:28448624

A prospective international observational prevalence study on prone positioning of ARDS patients: the APRONET (ARDS Prone Position Network) study.

PubMed

Guérin, C; Beuret, P; Constantin, J M; Bellani, G; Garcia-Olivares, P; Roca, O; Meertens, J H; Maia, P Azevedo; Becher, T; Peterson, J; Larsson, A; Gurjar, M; Hajjej, Z; Kovari, F; Assiri, A H; Mainas, E; Hasan, M S; Morocho-Tutillo, D R; Baboi, L; Chrétien, J M; François, G; Ayzac, L; Chen, L; Brochard, L; Mercat, A

2018-01-01

While prone positioning (PP) has been shown to improve patient survival in moderate to severe acute respiratory distress syndrome (ARDS) patients, the rate of application of PP in clinical practice still appears low. This study aimed to determine the prevalence of use of PP in ARDS patients (primary endpoint), the physiological effects of PP, and the reasons for not using it (secondary endpoints). The APRONET study was a prospective international 1-day prevalence study performed four times in April, July, and October 2016 and January 2017. On each study day, investigators in each ICU had to screen every patient. For patients with ARDS, use of PP, gas exchange, ventilator settings and plateau pressure (Pplat) were recorded before and at the end of the PP session. Complications of PP and reasons for not using PP were also documented. Values are presented as median (1st-3rd quartiles). Over the study period, 6723 patients were screened in 141 ICUs from 20 countries (77% of the ICUs were European), of whom 735 had ARDS and were analyzed. Overall 101 ARDS patients had at least one session of PP (13.7%), with no differences among the 4 study days. The rate of PP use was 5.9% (11/187), 10.3% (41/399) and 32.9% (49/149) in mild, moderate and severe ARDS, respectively (P = 0.0001). The duration of the first PP session was 18 (16-23) hours. Measured with the patient in the supine position before and at the end of the first PP session, PaO 2 /F I O 2 increased from 101 (76-136) to 171 (118-220) mmHg (P = 0.0001) driving pressure decreased from 14 [11-17] to 13 [10-16] cmH 2 O (P = 0.001), and Pplat decreased from 26 [23-29] to 25 [23-28] cmH 2 O (P = 0.04). The most prevalent reason for not using PP (64.3%) was that hypoxemia was not considered sufficiently severe. Complications were reported in 12 patients (11.9%) in whom PP was used (pressure sores in five, hypoxemia in two, endotracheal tube-related in two ocular in two, and a transient increase in intracranial pressure in one). In conclusion, this prospective international prevalence study found that PP was used in 32.9% of patients with severe ARDS, and was associated with low complication rates, significant increase in oxygenation and a significant decrease in driving pressure.

Nitric oxide leads to cytoskeletal reorganization in the retinal pigment epithelium under oxidative stress.

PubMed

Sripathi, Srinivas R; He, Weilue; Um, Ji-Yeon; Moser, Trevor; Dehnbostel, Stevie; Kindt, Kimberly; Goldman, Jeremy; Frost, Megan C; Jahng, Wan Jin

2012-01-01

Light is a risk factor for various eye diseases, including age-related macular degeneration (AMD) and retinitis pigmentosa (RP). We aim to understand how cytoskeletal proteins in the retinal pigment epithetlium (RPE) respond to oxidative stress, including light and how these responses affect apoptotic signaling. Previously, proteomic analysis revealed that the expression levels of vimentin and serine/threonine protein phosphatase 2A (PP2A) are significantly increased when mice are exposed under continuous light for 7 days compared to a condition of 12 hrs light/dark cycling exposure using retina degeneration 1 (rd1) model. When melatonin is administered to animals while they are exposed to continuous light, the levels of vimentin and PP2A return to a normal level. Vimentin is a substrate of PP2A that directly binds to vimentin and dephosphorylates it. The current study shows that upregulation of PP2Ac (catalytic subunit) phosphorylation negatively correlates with vimentin phosphorylation under stress condition. Stabilization of vimentin appears to be achieved by decreased PP2Ac phosphorylation by nitric oxide induction. We tested our hypothesis that site-specific modifications of PP2Ac may drive cytoskeletal reorganization by vimentin dephosphorylation through nitric oxide signaling. We speculate that nitric oxide determines protein nitration under stress conditions. Our results demonstrate that PP2A and vimentin are modulated by nitric oxide as a key element involved in cytoskeletal signaling. The current study suggests that external stress enhances nitric oxide to regulate PP2Ac and vimentin phosphorylation, thereby stabilizing or destabilizing vimentin. Phosphorylation may result in depolymerization of vimentin, leading to nonfilamentous particle formation. We propose that a stabilized vimentin might act as an anti-apoptotic molecule when cells are under oxidative stress.

Nitric oxide leads to cytoskeletal reorganization in the retinal pigment epithelium under oxidative stress

PubMed Central

Um, Ji-Yeon; Moser, Trevor; Dehnbostel, Stevie; Kindt, Kimberly; Goldman, Jeremy; Frost, Megan C.; Jahng, Wan Jin

2016-01-01

Light is a risk factor for various eye diseases, including age-related macular degeneration (AMD) and retinitis pigmentosa (RP). We aim to understand how cytoskeletal proteins in the retinal pigment epithetlium (RPE) respond to oxidative stress, including light and how these responses affect apoptotic signaling. Previously, proteomic analysis revealed that the expression levels of vimentin and serine/threonine protein phosphatase 2A (PP2A) are significantly increased when mice are exposed under continuous light for 7 days compared to a condition of 12 hrs light/dark cycling exposure using retina degeneration 1 (rd1) model. When melatonin is administered to animals while they are exposed to continuous light, the levels of vimentin and PP2A return to a normal level. Vimentin is a substrate of PP2A that directly binds to vimentin and dephosphorylates it. The current study shows that upregulation of PP2Ac (catalytic subunit) phosphorylation negatively correlates with vimentin phosphorylation under stress condition. Stabilization of vimentin appears to be achieved by decreased PP2Ac phosphorylation by nitric oxide induction. We tested our hypothesis that site-specific modifications of PP2Ac may drive cytoskeletal reorganization by vimentin dephosphorylation through nitric oxide signaling. We speculate that nitric oxide determines protein nitration under stress conditions. Our results demonstrate that PP2A and vimentin are modulated by nitric oxide as a key element involved in cytoskeletal signaling. The current study suggests that external stress enhances nitric oxide to regulate PP2Ac and vimentin phosphorylation, thereby stabilizing or destabilizing vimentin. Phosphorylation may result in depolymerization of vimentin, leading to nonfilamentous particle formation. We propose that a stabilized vimentin might act as an anti-apoptotic molecule when cells are under oxidative stress. PMID:27974994

Suggested Involvement of PP1/PP2A Activity and De Novo Gene Expression in Anhydrobiotic Survival in a Tardigrade, Hypsibius dujardini, by Chemical Genetic Approach.

PubMed

Kondo, Koyuki; Kubo, Takeo; Kunieda, Takekazu

2015-01-01

Upon desiccation, some tardigrades enter an ametabolic dehydrated state called anhydrobiosis and can survive a desiccated environment in this state. For successful transition to anhydrobiosis, some anhydrobiotic tardigrades require pre-incubation under high humidity conditions, a process called preconditioning, prior to exposure to severe desiccation. Although tardigrades are thought to prepare for transition to anhydrobiosis during preconditioning, the molecular mechanisms governing such processes remain unknown. In this study, we used chemical genetic approaches to elucidate the regulatory mechanisms of anhydrobiosis in the anhydrobiotic tardigrade, Hypsibius dujardini. We first demonstrated that inhibition of transcription or translation drastically impaired anhydrobiotic survival, suggesting that de novo gene expression is required for successful transition to anhydrobiosis in this tardigrade. We then screened 81 chemicals and identified 5 chemicals that significantly impaired anhydrobiotic survival after severe desiccation, in contrast to little or no effect on survival after high humidity exposure only. In particular, cantharidic acid, a selective inhibitor of protein phosphatase (PP) 1 and PP2A, exhibited the most profound inhibitory effects. Another PP1/PP2A inhibitor, okadaic acid, also significantly and specifically impaired anhydrobiotic survival, suggesting that PP1/PP2A activity plays an important role for anhydrobiosis in this species. This is, to our knowledge, the first report of the required activities of signaling molecules for desiccation tolerance in tardigrades. The identified inhibitory chemicals could provide novel clues to elucidate the regulatory mechanisms underlying anhydrobiosis in tardigrades.

Suggested Involvement of PP1/PP2A Activity and De Novo Gene Expression in Anhydrobiotic Survival in a Tardigrade, Hypsibius dujardini, by Chemical Genetic Approach

PubMed Central

Kondo, Koyuki; Kubo, Takeo; Kunieda, Takekazu

2015-01-01

Upon desiccation, some tardigrades enter an ametabolic dehydrated state called anhydrobiosis and can survive a desiccated environment in this state. For successful transition to anhydrobiosis, some anhydrobiotic tardigrades require pre-incubation under high humidity conditions, a process called preconditioning, prior to exposure to severe desiccation. Although tardigrades are thought to prepare for transition to anhydrobiosis during preconditioning, the molecular mechanisms governing such processes remain unknown. In this study, we used chemical genetic approaches to elucidate the regulatory mechanisms of anhydrobiosis in the anhydrobiotic tardigrade, Hypsibius dujardini. We first demonstrated that inhibition of transcription or translation drastically impaired anhydrobiotic survival, suggesting that de novo gene expression is required for successful transition to anhydrobiosis in this tardigrade. We then screened 81 chemicals and identified 5 chemicals that significantly impaired anhydrobiotic survival after severe desiccation, in contrast to little or no effect on survival after high humidity exposure only. In particular, cantharidic acid, a selective inhibitor of protein phosphatase (PP) 1 and PP2A, exhibited the most profound inhibitory effects. Another PP1/PP2A inhibitor, okadaic acid, also significantly and specifically impaired anhydrobiotic survival, suggesting that PP1/PP2A activity plays an important role for anhydrobiosis in this species. This is, to our knowledge, the first report of the required activities of signaling molecules for desiccation tolerance in tardigrades. The identified inhibitory chemicals could provide novel clues to elucidate the regulatory mechanisms underlying anhydrobiosis in tardigrades. PMID:26690982

[Quantification of Wood Flour and Polypropylene in Chinese Fir/Polypropylene Composites by FTIR].

PubMed

Lao, Wan-li; Li, Gai-yun; Zhou, Qun; Qin, Te-fu

2015-06-01

The ratio of wood and plastic in Wood Plastic Composites (WPCss) influences quality and price, but traditional thermochemical methods cannot rapidly and accurately quantify the ratio of wood/PP in WPCss. This paper was addressed to investigate the feasibility of quantifying the wood flour content and plastic content in WPCss by Fourier Transform Infrared (FTIR) spectroscopy. With Chinese fir, polypropylene (PP) and other additives as raw materials, 13 WPCs samples with different wood flour contents, ranging from 9.8% to 61.5%, were prepared by modifying wood flour, mixing materials and extrusion pelletizing. The samples were analyzed by FTIR with the KBr pellets technique. The absorption peaks of WPCss at 1059, 1 033 and 1 740 cm(-1) are considered as characteristic of Chinese fir, and the absorption peaks at 1 377, 2 839 and 841 cm(-1) are typical of PP by comparing the spectra of WPCss with that of Chinese fir, PP and other additives. The relationship between the wood flour content, PP content in WPCss and their characteristic IR peaks height ratio was established. The results show that there is a strong linear correlation between the wood flour content in WPCss and I1 059/l 1 377/I1 033, /I1377, R2 are 0.992 and 0.993 respectively; there is a high linear correlation between the PP content in WPCss and I1 377/I1 740, I2 839 /I1 740 R2 are 0.985 and 0.981, respectively. Quantitative methods of the wood flour content and PP content in WPCss by FTIR were developed, the predictive equations of the wood flour content in WPCss are y = 53.297x-9. 107 and y = 55.922x-10.238, the predictive equations of the PP content in WPCss are y = 6.828 5x+5.403 6 and y = 8.719 7x+3.295 8. The results of the accuracy test and precision test show that the method has strong repeatability and high accuracy. The average prediction relative deviations of the wood flour content and PP content in WPCss are about 5%. The prediction accuracy has been improved remarkably, compared to thermochemical methods. More importantly, FTIR is more easy-handing. This experiment may provide a simple, rapid and accurate method for quantification of wood flour and PP in Chinese fir/PP composites.

Progesterone-associated proteins PP12 and PP14 in the human endometrium.

PubMed

Rutanen, E M; Koistinen, R; Seppälä, M; Julkunen, M; Suikkari, A M; Huhtala, M L

1987-01-01

Two proteins, designated as PP12 and PP14 were originally isolated from soluble extracts of the human placenta and its adjacent membranes. We have shown that they are synthesized by decidualized/secretory endometrium and not by placenta. Both proteins occur at high concentrations in human amniotic fluid, which is therefore an excellent source for purification. PP12 is a 34-kDa glycoprotein, which has an N-terminal amino acid sequence of Ala-Pro-Trp-Gln-Cys-Ala-Pro-Cys-Ser-Ala. This is identical with that of somatomedin-binding protein purified from the amniotic fluid. PP12 too binds somatomedin-C, or IGF-I (insulin-like growth factor-I). Human secretory endometrium synthesizes and secretes PP12, and progesterone stimulates its secretion. PP14 is a 28-kDa glycoprotein. Its N-terminal sequence shows homology to that of beta-lactoglobulins from various species. We have found PP14 in the human endometrium, serum and milk. Immunologically, PP14 is related to progestagen-associated endometrial protein (PEP), alpha-2 pregnancy-associated endometrial protein (alpha-2, PEG), endometrial protein 15 (EP15), alpha-uterine protein (AUP) and chorionic alpha-2 microglobulin (CAG-2). In ovulatory menstrual cycles, the concentration of PP14 increases in endometrial tissue as the secretory changes advance. In serum, the PP14 concentration begins to rise later than the progesterone levels, and high serum PP14 levels are maintained for the first days of the next cycle. By contrast, no elevation of serum PP14 level is seen in anovulatory cycles. Our results show that progesterone-associated proteins are synthesized by the human endometrium and appear in the peripheral circulation, where they can be quantitatively measured using immunochemical techniques.

Evaluation of the immunogenicity and protective effects of a trivalent chimeric norovirus P particle immunogen displaying influenza HA2 from subtypes H1, H3 and B

PubMed Central

Gong, Xin; Yin, He; Shi, Yuhua; He, Xiaoqiu; Yu, Yongjiao; Guan, Shanshan; Kuai, Ziyu; Haji, Nasteha M; Haji, Nafisa M; Kong, Wei; Shan, Yaming

2016-01-01

The ectodomain of the influenza A virus (IAV) hemagglutinin (HA) stem is highly conserved across strains and has shown promise as a universal influenza vaccine in a mouse model. In this study, potential B-cell epitopes were found through sequence alignment and epitope prediction in a stem fragment, HA2:90-105, which is highly conserved among virus subtypes H1, H3 and B. A norovirus (NoV) P particle platform was used to express the HA2:90-105 sequences from subtypes H1, H3 and B in loops 1, 2 and 3 of the protrusion (P) domain, respectively. Through mouse immunization and microneutralization assays, the immunogenicity and protective efficacy of the chimeric NoV P particle (trivalent HA2-PP) were tested against infection with three subtypes (H1N1, H3N2 and B) of IAV in Madin–Darby canine kidney cells. The protective efficacy of the trivalent HA2-PP was also evaluated preliminarily in vivo by virus challenge in the mouse model. The trivalent HA2-PP immunogen induced significant IgG antibody responses, which could be enhanced by a virus booster vaccination. Moreover, the trivalent HA2-PP immunogen also demonstrated in vitro neutralization of the H3 and B viruses, and in vivo protection against the H3 virus. Our results support the notion that a broadly protective vaccine approach using an HA2-based NoV P particle platform can provide cross-protection against challenge viruses of different IAV subtypes. The efficacy of the immunogen should be further enhanced for practicality, and a better understanding of the protective immune mechanism will be critical for the development of HA2-based multivalent vaccines. PMID:27222326

Monitoring autophagic flux using p62/SQSTM1 based luciferase reporters in glioma cells.

PubMed

Min, Zhang; Ting, Yao; Mingtao, Gong; Xiaofei, Tang; Dong, Yan; Chenguang, Zhang; Wei, Ding

2018-02-01

Autophagy is a highly dynamic process characterized with the term of autophagic flux. In the present study, we developed a quantifiable luciferase reporter system to measure the capacity as well as the dynamics of autophagic flux. Briefly, a luciferase variant of Luc2p was fused with p62/SQSTM1 or its UBA domain deletion mutant (p62ΔU) and transfected into cells. The expressed Luc2p-p62 fusion protein was primarily degraded via autophagy, while Luc2p-p62ΔU was employed as a normalization control due to its resistance to autophagic degradation. The luciferase activity of the lysates from two parallel populations of glioma cells expressing either Luc2p-p62 or Luc2p-p62ΔU was determined and the ratio of Luc2p-p62ΔU/Luc2p-p62 was used to assay the autophagic flux. By this approach, the induction of autophagy was manifested as an increased Luc2p-p62ΔU/Luc2p-p62 ratio, which could be neutralized by autophagy inhibitors or knockdown of ATG5. The performance of our autophagic flux detection system was comparable to a recently reported GFP-LC3-RFP-LC3ΔG probe. We tested the system in TMZ treated glioma cells, and found that coadministration of chloroquine to attenuate cellular autophagic flux significantly improved the TMZ efficacy by triggering more early apoptosis. Collectively, our luciferase-based autophagic flux assay may serve as a useful alternative yet sensitive method for autophagic flux detection in tumor cells. Copyright © 2018 Elsevier Inc. All rights reserved.

Adaptation of HepG2 cells to a steady-state reduction in the content of protein phosphatase 6 (PP6) catalytic subunit

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boylan, Joan M.; Salomon, Arthur R.; Department of Chemistry, Brown University, Providence, RI

Protein phosphatase 6 (PP6) is a ubiquitous Ser/Thr phosphatase involved in an array of cellular processes. To assess the potential of PP6 as a therapeutic target in liver disorders, we attenuated expression of the PP6 catalytic subunit in HepG2 cells using lentiviral-transduced shRNA. Two PP6 knock-down (PP6KD) cell lines (90% reduction of PP6-C protein content) were studied in depth. Both proliferated at a rate similar to control cells. However, flow cytometry indicated G2/M cell cycle arrest that was accounted for by a shift of the cells from a diploid to tetraploid state. PP6KD cells did not show an increase inmore » apoptosis, nor did they exhibit reduced viability in the presence of bleomycin or taxol. Gene expression analysis by microarray showed attenuated anti-inflammatory signaling. Genes associated with DNA replication were downregulated. Mass spectrometry-based phosphoproteomic analysis yielded 80 phosphopeptides representing 56 proteins that were significantly affected by a stable reduction in PP6-C. Proteins involved in DNA replication, DNA damage repair and pre-mRNA splicing were overrepresented among these. PP6KD cells showed intact mTOR signaling. Our studies demonstrated involvement of PP6 in a diverse set of biological pathways and an adaptive response that may limit the effectiveness of targeting PP6 in liver disorders. - Highlights: • Lentiviral-transduced shRNA was used to generate a stable knockdown of PP6 in HepG2 cells. • Cells adapted to reduced PP6; cell proliferation was unaffected, and cell survival was normal. • However, PP6 knockdown was associated with a transition to a tetraploid state. • Genomic profiling showed downregulated anti-inflammatory signaling and DNA replication. • Phosphoproteomic profiling showed changes in proteins associated with DNA replication and repair.« less

Polysaccharide-inducible endoglucanases from Lentinula edodes exhibit a preferential hydrolysis of 1,3-1,4-β-glucan and xyloglucan.

PubMed

Takeda, Takumi; Nakano, Yuki; Takahashi, Machiko; Sakamoto, Yuichi; Konno, Naotake

2013-08-07

Three genes encoding glycoside hydrolase family 12 (GH12) enzymes from Lentinula edodes, namely Lecel12A, Lecel12B, and Lecel12C, were newly cloned by PCR using highly conserved sequence primers. To investigate enzymatic properties, recombinant enzymes encoded by L. edodes DNAs and GH12 genes from Postia placenta (PpCel12A and PpCel12B) and Schizophyllum commune (ScCel12A) were prepared in Brevibacillus choshinensis. Recombinant LeCel12A, PpCel12A, and PpCel12B, which were grouped in GH12 subfamily 1, preferentially hydrolyzed 1,3-1,4-β-glucan. By contrast, LeCel12B, LeCel12C, and ScCel12A, members of the subfamily 2, exhibited specific hydrolysis of xyloglucan. These results suggest that two subfamilies of GH12 are separated based on the substrate specificity. Transcript levels of L. edodes genes increased 72 h after growth of L. edodes mycelia cells in the presence of plant cell wall polymers such as xyloglucan, 1,3-1,4-β-glucan, and cellulose. These results suggest that L. edodes GH12 enzymes have evolved to hydrolyze 1,3-1,4-β-glucan and xyloglucan, which might enhance hyphal extension and nutrient acquisition.

I(2)(PP2A) regulates p53 and Akt correlatively and leads the neurons to abort apoptosis.

PubMed

Liu, Gong-Ping; Wei, Wei; Zhou, Xin; Zhang, Yao; Shi, Hai-Hong; Yin, Jun; Yao, Xiu-Qing; Peng, Cai-Xia; Hu, Juan; Wang, Qun; Li, Hong-Lian; Wang, Jian-Zhi

2012-02-01

A chronic neuron loss is the cardinal pathology in Alzheimer disease (AD), but it is still not understood why most neurons in AD brain do not accomplish apoptosis even though they are actually exposed to an environment with enriched proapoptotic factors. Protein phosphatase-2A inhibitor-2 (I(2)(PP2A)), an endogenous PP2A inhibitor, is significantly increased in AD brain, but the role of I(2)(PP2A) in AD-like neuron loss is elusive. Here, we show that I(2)(PP2A) regulates p53 and Akt correlatively. The mechanisms involve activated transcription and p38 MAPK activities. More importantly, we demonstrate that the simultaneous activation of Akt induced by I(2)(PP2A) counteracts the hyperactivated p53-induced cell apoptosis. Furthermore, I(2)(PP2A), p53 and Akt are all elevated in the brain of mouse model and AD patients. Our results suggest that the increased I(2)(PP2A) may trigger apoptosis by p53 upregulation, but due to simultaneous activation of Akt, the neurons are aborted from the apoptotic pathway. This finding contributes to the understanding of why most neurons in AD brain do not undergo apoptosis. Copyright © 2010. Published by Elsevier Inc.

Pathologic significance of SET/I2PP2A-mediated PP2A and non-PP2A pathways in polycystic ovary syndrome (PCOS).

PubMed

Jiang, Shi-Wen; Xu, Siliang; Chen, Haibin; Liu, Xiaoqiang; Tang, Zuoqing; Cui, Yugui; Liu, Jiayin

2017-01-01

SET (SE translocation, SET), a constitutive inhibitor of protein phosphatase 2A (PP2A), is a multifunctional oncoprotein involved in DNA replication, histone modification, nucleosome assembly, gene transcription and cell proliferation. It is widely expressed in human tissues including the gonadal system and brain. Intensive studies have shown that overexpressed SET plays an important role in the development of Alzheimer's disease (AD), and may also contribute to the malignant transformation of breast and ovarian cancers. Recent studies indicated that through interaction with PP2A, SET may upregulate androgen biosynthesis and contribute to hyperandrogenism in polycystic ovary syndrome (PCOS) patients. This review article summarizes data concerning the SET expression in ovaries from PCOS and normal women, and analyzes the role/regulatory mechanism of SET for androgen biosynthesis in PCOS, as well as the significance of this action in the development of PCOS. The potential value of SET-triggered pathway as a therapeutic target and the application of anti-SET reagents for treating hyperandrogenism in PCOS patients are also discussed. Copyright © 2016. Published by Elsevier B.V.

Protein phosphatase 2A inhibition and subsequent cytoskeleton reorganization contributes to cell migration caused by microcystin-LR in human laryngeal epithelial cells (Hep-2).

PubMed

Wang, Beilei; Liu, Jinghui; Huang, Pu; Xu, Kailun; Wang, Hanying; Wang, Xiaofeng; Guo, Zonglou; Xu, Lihong

2017-03-01

The major toxic mechanism of Microcystin-LR is inhibition of the activity of protein phosphatase 2A (PP2A), resulting in a series of cytotoxic effects. Our previous studies have demonstrated that microcystin-LR (MCLR) induced very different molecular effects in normal cells and the tumor cell line SMMC7721. To further explore the MCLR toxicity mechanism in tumor cells, human laryngeal epithelial cells (Hep-2) was examined in this study. Western blot, immunofluorescence, immunoprecipitation, and transwell migration assay were used to detect the effects of MCLR on PP2A activity, PP2A substrates, cytoskeleton, and cell migration. The results showed that the protein level of PP2A subunits and the posttranslational modification of the catalytic subunit were altered and that the binding of the AC core enzyme as well as the binding of PP2A/C and α4, was also affected. As PP2A substrates, the phosphorylation of MAPK pathway members, p38, ERK1/2, and the cytoskeleton-associated proteins, Hsp27, VASP, Tau, and Ezrin were increased. Furthermore, MCLR induced reorganization of the cytoskeleton and promoted cell migration. Taken together, direct covalent binding to PP2A/C, alteration of the protein levels and posttranslational modification, as well as the binding of subunits, are the main pattern for the effects of MCLR on PP2A in Hep-2. A dose-dependent change in p-Tau and p-Ezrin due to PP2A inhibition may contribute to the changes in the cytoskeleton and be related to the cell migration in Hep-2. Our data provide a comprehensive exposition of the MCLR mechanism on tumor cells. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 890-903, 2017. © 2016 Wiley Periodicals, Inc.

Effects of elastic bands on force and power characteristics during the back squat exercise.

PubMed

Wallace, Brian J; Winchester, Jason B; McGuigan, Michael R

2006-05-01

Athletes commonly use elastic bands as a training method to increase strength and performance. The purpose of this study was to investigate the effect of elastic bands on peak force (PF), peak power (PP), and peak rate of force development (RFD) during the back-squat exercise (BSE). Ten recreationally resistance-trained subjects (4 women, 6 men, mean age 21.3 +/- 1.5 years) were tested for their 1 repetition maximum (1RM) in the BSE (mean 117.6 +/- 48.2 kg) on a Smith machine. Testing was performed on 2 separate days, with 2 sets of 3 repetitions being performed for each condition. Testing was conducted at 60% and 85% of 1RM with and without using elastic bands. In addition, 2 elastic band loading conditions were tested (B1 and B2) at each of the 2 resistances. No bands (NB) represents where all of the resistance was acquired from free-weights. B1 represents where approximately 80% of the resistance was provided by free-weights, and approximately 20% was provided by bands. B2 represents where approximately 65% of the resistance was provided by free-weights, and approximately 35% was provided from bands. The subjects completed the BSE under each condition, whereas PF, PP, and RFD was recorded using a force platform. There was a significant (p < 0.05) increase in PF between NB-85 and B2-85 of 16%. Between B1-85 and B2-85, PF was increased significantly by 5% (p < 0.05). There was a significant (p < 0.05) increase in PP between NB-85 and B2-85 of 24%. No significant differences were observed in RFD during the 85% conditions or for any of the measured variables during the 60% conditions (p < 0.05). The results suggest that the use of elastic bands in conjunction with free weights can significantly increase PF and PP during the BSE over free-weight resistance alone under certain loading conditions. The greatest differences are observed during the higher loading conditions, with the B1-85 condition appearing to be optimal for athletic performance of the ones we tested. The strength training professional could use variable resistance training (VRT) to increase PF and PP more than the traditional BSE can. VRT could also be used to train these 2 performance characteristics together, which might be especially useful in season, when weight-room training volume can sometimes be limited.

Intermittent Induction of HIF-1α Produces Lasting Effects on Malignant Progression Independent of Its Continued Expression

PubMed Central

Choi, Hyunsung; Gillespie, David L.; Berg, Shauna; Rice, Christopher; Couldwell, Sandrine; Gu, Jie; Colman, Howard; Jensen, Randy L.; Huang, L. Eric

2015-01-01

Dysregulation of hypoxia-inducible transcription factors HIF-1α and HIF-2α correlates with poor prognosis in human cancers; yet, divergent and sometimes opposing activities of these factors in cancer biology have been observed. Adding to this complexity is that HIF-1α apparently possesses tumor-suppressing activities, as indicated by the loss-of-function mutations or even homozygous deletion of HIF1A in certain human cancers. As a step towards understanding this complexity, we employed 8-week intermittent induction of a stable HIF-1α variant, HIF1α(PP), in various cancer cell lines and examined the effects on malignant progression in xenografts of immunocompromised mice in comparison to those of HIF2α(PP). Although 8-week treatment led to eventual loss of HIF1α(PP) expression, treated osteosarcoma U-2 OS cells acquired tumorigenicity in the subcutaneous tissue. Furthermore, the prior treatment resulted in widespread invasion of malignant glioma U-87 MG cells in the mouse brain and sustained growth of U-118 MG glioma cells. The lasting effects of HIF-1α on malignant progression are specific because neither HIF2α(PP) nor β-galactosidase yielded similar effects. By contrast, transient expression of HIF1α(PP) in U-87 MG cells or constitutive expression of HIF1α(PP) but not HIF2α(PP) in a patient-derived glioma sphere culture inhibited tumor growth and spread. Our results indicate that intermittent induction of HIF-1α produces lasting effects on malignant progression even at its own expense. PMID:25893706

Absence of ppGpp Leads to Increased Mobilization of Intermediately Accumulated Poly(3-Hydroxybutyrate) in Ralstonia eutropha H16

PubMed Central

Juengert, Janina R.; Borisova, Marina; Wolz, Christiane; Brigham, Christopher J.; Sinskey, Anthony J.

2017-01-01

ABSTRACT In this study, we constructed a set of Ralstonia eutropha H16 strains with single, double, or triple deletions of the (p)ppGpp synthase/hydrolase (spoT1), (p)ppGpp synthase (spoT2), and/or polyhydroxybutyrate (PHB) depolymerase (phaZa1 or phaZa3) gene, and we determined the impact on the levels of (p)ppGpp and on accumulated PHB. Mutants with deletions of both the spoT1 and spoT2 genes were unable to synthesize detectable amounts of (p)ppGpp and accumulated only minor amounts of PHB, due to PhaZa1-mediated depolymerization of PHB. In contrast, unusually high levels of PHB were found in strains in which the (p)ppGpp concentration was increased by the overexpression of (p)ppGpp synthase (SpoT2) and the absence of (p)ppGpp hydrolase. Determination of (p)ppGpp levels in wild-type R. eutropha under different growth conditions and induction of the stringent response by amino acid analogs showed that the concentrations of (p)ppGpp during the growth phase determine the amount of PHB remaining in later growth phases by influencing the efficiency of the PHB mobilization system in stationary growth. The data reported for a previously constructed ΔspoT2 strain (C. J. Brigham, D. R. Speth, C. Rha, and A. J. Sinskey, Appl Environ Microbiol 78:8033–8044, 2012, https://doi.org/10.1128/AEM.01693-12) were identified as due to an experimental error in strain construction, and our results are in contrast to the previous indication that the spoT2 gene product is essential for PHB accumulation in R. eutropha. IMPORTANCE Polyhydroxybutyrate (PHB) is an important intracellular carbon and energy storage compound in many prokaryotes and helps cells survive periods of starvation and other stress conditions. Research activities in several laboratories over the past 3 decades have shown that both PHB synthase and PHB depolymerase are constitutively expressed in most PHB-accumulating bacteria, such as Ralstonia eutropha. This implies that PHB synthase and depolymerase activities must be well regulated in order to avoid a futile cycle of simultaneous PHB synthesis and PHB degradation (mobilization). Previous reports suggested that the stringent response in Rhizobium etli and R. eutropha is involved in the regulation of PHB metabolism. However, the levels of (p)ppGpp and the influence of those levels on PHB accumulation and PHB mobilization have not yet been determined for any PHB-accumulating species. In this study, we optimized a (p)ppGpp extraction procedure and a high-performance liquid chromatography–mass spectrometry (HPLC-MS)-based detection method for the quantification of (p)ppGpp in R. eutropha. This enabled us to study the relationship between the concentrations of (p)ppGpp and the accumulated levels of PHB in the wild type and in several constructed mutant strains. We show that overproduction of the alarmone (p)ppGpp correlated with reduced growth and massive overproduction of PHB. In contrast, in the absence of (p)ppGpp, mobilization of PHB was dramatically enhanced. PMID:28455332

Crizotinib in patients with anaplastic lymphoma kinase-positive advanced non-small cell lung cancer versus chemotherapy as a first-line treatment.

PubMed

Zhou, Jianya; Zheng, Jing; Zhang, Xiaochen; Zhao, Jing; Zhu, Yanping; Shen, Qian; Wang, Yuehong; Sun, Ke; Zhang, Zeying; Pan, Zhijie; Shen, Yihong; Zhou, Jianying

2018-01-03

To compare the efficacy of crizotinib, pemetrexed and other chemotherapy regimens as a first-line treatment in patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) in real world clinical use and to evaluate the +86-571-87,236,876 predictive clinical factors of the efficacy of crizotinib. The 73 patients with ALK-positive advanced NSCLC were divided into three groups based on the first-line treatment: first-line crizotinib group (1-CRZ group, n = 32); first-line platinum-based pemetrexed treatment group (1-PP group, n = 28), and first-line chemotherapy platinum-based non-pemetrexed group (N1-PP, n = 12). Sixty eight of the 73 patients received crizotinib treatment and followed up in our hospital. Differences in the objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS) were compared in the different groups. The clinical factors were evaluated to predict the efficacy of crizotinib by the Kaplan-Meier survival analysis and Cox proportional hazards model. The PFS, ORR, DCR were 16.1 months, 78.1% (25/32) and 100% (32/32) in the 1-CRZ group; were 6.0 months, 17.9% (5/28) and 57.2% (16/28) in the 1-PP group; and were 2.9 months, 15.4% (2/13) and 46.2% (6/13) in the N1-PP group. The PFS of the 1-CRZ group was significantly longer than that of the 1-PP group (P < 0.001) and the N1-PP group (P < 0.001). The ORR and DCR of the 1-CRZ group was significantly greater than that of the 1-PP group and the N1-PP group (all the P < 0.001). Higher Eastern Cooperative Oncology Group (ECOG) performance status score (> = 2) (HR 2.345, 95% CI 1.137-4.834, P = 0.021) and patients received crizotinib after N1-PP chemotherapy (HR 2.345, 95% CI 1.137-4.834, P = 0.021) were two factors associated with shorter PFS after crizotinib treatment. In patients with ALK-positive NSCLC who did not receive previous treatment, crizotinib was superior to standard chemotherapy for the longer PFS and greater ORR and DCR. Higher ECOG score (> = 2) and patients received crizotinib after N1-PP chemotherapy predict poor efficacy of crizotinib.

Protein Phosphatase 2A Signaling in Human Prostate Cancer

DTIC Science & Technology

2011-06-01

centrifugation, 25 mL of supernatant was transferred to an assay plate; 100 mL of Malachite Green phosphate detection solution was added and incu...prostate cancer cells was resolved and immunoblotted for PP2AC and b-actin (internal control). PP2A activity was determined by malachite green–based

Impact of kerosene heater usage on indoor NO/sub 2/ exposures in 50 East Tennessee homes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dudney, C.S.; Hawthorne, A.R.; Monar, K.P.

1988-01-01

As part of a study of indoor air quality in 300 houses in Roane County, Tennessee, a special study was made on kerosene heater usage and indoor pollutant levels, with emphasis on NO/sub 2/. Owners of 45 homes with kerosene heaters deployed pairs of passive NO/sub 2/ monitors on a weekly basis for ten weeks and recorded the weekly amount of heater use. Without correcting for house-specific factors, such as air exchange rate, indoor NO/sub 2/ levels were found to increase about 0.3 ppB per h/week of homeowner-reported heater use. In the absence of heater use, NO/sub 2/ levels weremore » about 10 ppB in houses with and without kerosene heaters. In four houses with kerosene heaters and one house without, continuous measurements were made of NO, NO/sub x/, SO/sub 2/, and CO. CO and SO/sub 2/ levels increased threefold and tenfold, respectively, when the heater was operated compared to when it was off. Mean SO/sub 2/ levels during heater operation were 57, 46, and 110 ppB in three houses with radiant heaters and 13.5 ppB in one house with a convective heater. 5 refs., 8 figs., 3 tabs.« less

Role of GABAergic neurones in the nucleus tractus solitarii in modulation of cardiovascular activity.

PubMed

Zubcevic, Jasenka; Potts, Jeffrey T

2010-09-01

GABAergic neurones are interspersed throughout the nucleus tractus solitarii (NTS), and their tonic activity is crucial to the maintenance of cardiorespiratory homeostasis. However, the mechanisms that regulate the magnitude of GABAergic inhibition in the NTS remain unknown. We hypothesized that the level of GABAergic inhibition is proportionally regulated by the level of excitatory synaptic input to the NTS from baroreceptors. Using the in situ working heart-brainstem preparation in normotensive and spontaneously hypertensive rats, we blocked GABA(A) receptor-mediated neurotransmission in the NTS with gabazine (a specific GABA(A) receptor antagonist) at two levels of perfusion pressure (low PP, 60-70 mmHg; and high PP, 105-125 mmHg) while monitoring the immediate changes in cardiorespiratory variables. In normotensive rats, gabazine produced an immediate bradycardia consistent with disinhibition of NTS circuit neurones that regulate heart rate (HR) which was proportional to the level of arterial pressure (HR at low PP, 57 +/- 9 beats min(1); at high PP, 177 +/- 9 beats min(1); P < 0.001), suggesting that GABAergic circuitry in the NTS modulating heart rate was arterial pressure dependent. In contrast, there was no significant difference in the magnitude of gabazine-induced bradycardia in spontaneously hypertensive rats at low or high PP (HR at low PP, 45 +/- 10 beats min(1); at high PP, 58 +/- 7 beats min(1)). With regard to thoracic sympathetic nerve activity (tSNA), at high PP there was a significant reduction in tSNA during the inspiratory (I) phase of the respiratory cycle, but only in the normotensive rat (tSNA = 18.7 +/- 10%). At low PP, gabazine caused an elevation of the postinspiration phase of tSNA in both normotensive (tSNA = 23.7 +/- 2.9%) and hypertensive rats (tSNA = 44.2 +/- 14%). At low PP, gabazine produced no change in tSNA during the mid-expiration phase in either rat strain, but at high PP we observed a significant reduction in the mid-expiration phase tSNA, but only in the spontaneously hypertensive rat (tSNA = 25.2 +/- 8%). Gabazine at both low and high PP produced a reduction in the late expiration phase of tSNA in the hypertensive rat (low PP, tSNA = 29.4 +/- 4.4%; high PP, tSNA = 22.8 +/- 3%), whereas in the normotensive rat this was only significant at high PP (tSNA = 42.5 +/- 6.1%). Therefore, in the spontaneously hypertensive rat, contrary to the GABA(A) receptor-mediated control of HR, it appears that GABA(A) receptor-mediated control of tSNA in the NTS is arterial pressure dependent. This study provides new insight into the origin of GABAergic inhibition in NTS circuitry affecting heart rate and sympathetic activity.

An aqueous fluorescent sensor for Pb2+ based on phenothiazine-polyamide.

PubMed

Xie, Yadian; Li, Han; Liu, Xingliang; Wang, Zhaoqian; Lv, Haitang; Cao, Jianfang; Zhang, Chao; Jia, Qiangqiang; Han, Aixia

2018-04-30

A sensitive and selective fluorescent sensor for Pb 2+ ion based on phenothiazine-polyamide was built (named sensor PP). Due to introducing of four diethanolamine groups to polyamide, this sensor was totally water soluble. PP could detect Pb 2+ ion within 1 min in the presence of other metal ions in aqueous solution, the detect limit was 9.11 × 10 -8  M. Copyright © 2018 Elsevier B.V. All rights reserved.

Supercritical CO2 foaming of radiation crosslinked polypropylene/high-density polyethylene blend: Cell structure and tensile property

NASA Astrophysics Data System (ADS)

Yang, Chenguang; Xing, Zhe; Zhang, Mingxing; Zhao, Quan; Wang, Mouhua; Wu, Guozhong

2017-12-01

A blend of isotactic polypropylene (PP) with high-density polyethylene (HDPE) in different PP/HDPE ratios was irradiated by γ-ray to induce cross-linking and then foamed using supercritical carbon dioxide (scCO2) as a blowing agent. Radiation effect on the melting point and crystallinity were analyzed in detail. The average cell diameter and cell density were compared for PP/HDPE foams prepared under different conditions. The optimum absorbed dose for the scCO2 foaming of PP/HDPE in terms of foaming ability and cell structure was 20 kGy. Tensile measurements showed that the elongation at break and tensile strength at break of the crosslinked PP/HDPE foams were higher than the non-crosslinked ones. Of particular interest was the increase in the foaming temperature window from 4 ℃ for pristine PP to 8-12 ℃ for the radiation crosslinked PP/HDPE blends. This implies much easier handling of scCO2 foaming of crosslinked PP with the addition of HDPE.

Protein phosphatase 2ACα gene knock-out results in cortical atrophy through activating hippo cascade in neuronal progenitor cells.

PubMed

Liu, Bo; Sun, Li-Hua; Huang, Yan-Fei; Guo, Li-Jun; Luo, Li-Shu

2018-02-01

Protein phosphatase 2ACα (PP2ACα), a vital member of the protein phosphatase family, has been studied primarily as a regulator for the development, growth and protein synthesis of a lot of cell types. Dysfunction of PP2ACα protein results in neurodegenerative disease; however, this finding has not been directly confirmed in the mouse model with PP2ACα gene knock-out. Therefore, in this study presented here, we generated the PP2ACα gene knock-out mouse model by the Cre-loxP targeting gene system, with the purpose to directly observe the regulatory role of PP2ACα gene in the development of mouse's cerebral cortex. We observe that knocking-out PP2ACα gene in the central nervous system (CNS) results in cortical neuronal shrinkage, synaptic plasticity impairments, and learning/memory deficits. Further study reveals that PP2ACα gene knock-out initiates Hippo cascade in cortical neuroprogenitor cells (NPCs), which blocks YAP translocation into the nuclei of NPCs. Notably, p73, directly targeted by Hippo cascade, can bind to the promoter of glutaminase2 (GLS2) that plays a dominant role in the enzymatic regulation of glutamate/glutamine cycle. Finally, we find that PP2ACα gene knock-out inhibits the glutamine synthesis through up-regulating the activity of phosphorylated-p73 in cortical NPCs. Taken together, it concludes that PP2ACα critically supports cortical neuronal growth and cognitive function via regulating the signaling transduction of Hippo-p73 cascade. And PP2ACα indirectly modulates the glutamine synthesis of cortical NPCs through targeting p73 that plays a direct transcriptional regulatory role in the gene expression of GLS2. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of Photon Radiations in Semi-Rigid Artificial Tissue Sensitized by Protoporphyrin IX Encapsulated with Silica Nanoparticles

NASA Astrophysics Data System (ADS)

Makhadmeh, Ghaseb N.; Aziz, Azlan Abdul; Razak, Khairunisak Abdul; Al-Akhras, M.-Ali H.

2018-02-01

This study involves the synthesis of Protoporphyrin IX (PpIX) encapsulated with Silica Nanoparticles (SiNPs) as an application for Photodynamic therapy. Semi-rigid artificial tissues with optical features similar to human tissue were used as sample materials to ascertain the efficacy of PpIX encapsulated with SiNPs. The disparity in optical characteristics (transmittance, reflectance, scattering, and absorption) of tissues treated with encapsulated PpIX and naked PpIX under light exposure (Intensity at 408 nm ~1.19 mW/cm2) was explored. The optimal exposure times required for naked PpIX and SiNPs encapsulated PpIX to engulf Red Blood Cells (RBCs) in the artificial tissue were subsequently measured. Comparative analysis showed that the encapsulated PpIX has a 91.5 % higher efficacy than naked PpIX. The results prove the applicability of PpIX encapsulated with SiNP on artificial tissue and possible use on human tissue.

Uranium hydrogeochemical and stream sediment reconnaissance of the Newcastle NTMS quadrangle, Wyoming, including concentrations of forty-two additional elements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goff, S.J.; Sandoval, W.F.; Gallimore, D.L.

1980-06-01

During the summer and fall of 1977, 533 water and 1226 sediment samples were collected from 1740 locations within the 18,000 km/sup 2/ area of the Newcastle quadrangle, Wyoming. Water samples were collected from wells and springs; sediment samples were collected from stream channels and from springs. Each water sample was analyzed for uranium, and each sediment sample was analyzed for 43 elements, including uranium and thorium. Uranium concentrations in water samples range from below the detection limit of 0.02 ppB to 702.26 ppB and have a median of 1.73 ppB and a mean of 11.76 ppB. Water samples containingmore » high uranium concentrations (>20 ppB) generally are associated with known uranium mining activity or units known to be uranium bearing. About one-third of the water samples containing high uranium concentrations were collected from locations within the Pumpkin Buttes and Turnercrest-Ross Districts. Nearly half of the water samples containing high uranium concentrations were collected from locations just west of the Monument Hill and Highland Flats-Box Creek Districts. Similar anomalous uranium concentrations in this region have been reported updip from Exxon's Highland uranium deposits. High uranium concentrations were also found associated with the Lance Creek-Old Woman Anticline District.« less

Measurement of Prompt $$\\psi(2S) \\to J/\\psi$$ Yield Ratios in Pb-Pb and $p-p$ Collisions at $$\\sqrt {s_{NN}}=$$ 2.76 TeV

DOE PAGES

Khachatryan, Vardan

2014-12-31

The ratio between the prompt ψ(2S) and J/ψ yields, reconstructed via their decays into μ +μ -, is measured in Pb-Pb and p-p collisions at √s NN=2.76 TeV. Likewise, the analysis is based on Pb-Pb and p-p data samples collected by CMS at the Large Hadron Collider, corresponding to integrated luminosities of 150 μb -1 and 5.4 pb -1, respectively. The double ratio of measured yields (N ψ(2S)/N J/ψ) Pb-Pb/(Nψ(2S)/N J/ψ) p-p is computed in three Pb-Pb collision centrality bins and two kinematic ranges: one at midrapidity, |y|<1.6, covering the transverse momentum range 6.5T<30 GeV/c, and the other at forwardmore » rapidity, 1.6<|y|<2.4, extending to lower p T values, 3T<30 GeV/c. Furthermore, the centrality-integrated double ratio changes from 0.45±0.13(stat)±0.07(syst) in the first range to 1.67±0.34(stat)±0.27(syst) in the second. This difference is most pronounced in the most central collisions.« less

The Efficiency of Dentin Sialoprotein-Phosphophoryn Processing Is Affected by Mutations Both Flanking and Distant from the Cleavage Site*

PubMed Central

Yang, Robert T.; Lim, Glendale L.; Dong, Zhihong; Lee, Arthur M.; Yee, Colin T.; Fuller, Robert S.; Ritchie, Helena H.

2013-01-01

Normal dentin mineralization requires two highly acidic proteins, dentin sialoprotein (DSP) and phosphophoryn (PP). DSP and PP are synthesized as part of a single secreted precursor, DSP-PP, which is conserved in marsupial and placental mammals. Using a baculovirus expression system, we previously found that DSP-PP is accurately cleaved into DSP and PP after secretion into medium by an endogenous, secreted, zinc-dependent Sf9 cell activity. Here we report that mutation of conserved residues near and distant from the G447↓D448 cleavage site in DSP-PP240 had dramatic effects on cleavage efficiency by the endogenous Sf9 cell processing enzyme. We found that: 1) mutation of residues flanking the cleavage site from P4 to P4′ blocked, impaired, or enhanced DSP-PP240 cleavage; 2) certain conserved amino acids distant from the cleavage site were important for precursor cleavage; 3) modification of the C terminus by appending a C-terminal tag altered the pattern of processing; and 4) mutations in DSP-PP240 had similar effects on cleavage by recombinant human BMP1, a candidate physiological processing enzyme, as was seen with the endogenous Sf9 cell activity. An analysis of a partial TLR1 cDNA from Sf9 cells indicates that residues that line the substrate-binding cleft of Sf9 TLR1 and human BMP1 are nearly perfectly conserved, offering an explanation of why Sf9 cells so accurately process mammalian DSP-PP. The fact that several mutations in DSP-PP240 significantly modified the amount of PP240 product generated from DSP-PP240 precursor protein cleavage suggests that such mutation may affect the mineralization process. PMID:23297400

The efficiency of dentin sialoprotein-phosphophoryn processing is affected by mutations both flanking and distant from the cleavage site.

PubMed

Yang, Robert T; Lim, Glendale L; Dong, Zhihong; Lee, Arthur M; Yee, Colin T; Fuller, Robert S; Ritchie, Helena H

2013-02-22

Normal dentin mineralization requires two highly acidic proteins, dentin sialoprotein (DSP) and phosphophoryn (PP). DSP and PP are synthesized as part of a single secreted precursor, DSP-PP, which is conserved in marsupial and placental mammals. Using a baculovirus expression system, we previously found that DSP-PP is accurately cleaved into DSP and PP after secretion into medium by an endogenous, secreted, zinc-dependent Sf9 cell activity. Here we report that mutation of conserved residues near and distant from the G(447)↓D(448) cleavage site in DSP-PP(240) had dramatic effects on cleavage efficiency by the endogenous Sf9 cell processing enzyme. We found that: 1) mutation of residues flanking the cleavage site from P(4) to P(4)' blocked, impaired, or enhanced DSP-PP(240) cleavage; 2) certain conserved amino acids distant from the cleavage site were important for precursor cleavage; 3) modification of the C terminus by appending a C-terminal tag altered the pattern of processing; and 4) mutations in DSP-PP(240) had similar effects on cleavage by recombinant human BMP1, a candidate physiological processing enzyme, as was seen with the endogenous Sf9 cell activity. An analysis of a partial TLR1 cDNA from Sf9 cells indicates that residues that line the substrate-binding cleft of Sf9 TLR1 and human BMP1 are nearly perfectly conserved, offering an explanation of why Sf9 cells so accurately process mammalian DSP-PP. The fact that several mutations in DSP-PP(240) significantly modified the amount of PP(240) product generated from DSP-PP(240) precursor protein cleavage suggests that such mutation may affect the mineralization process.

AbetaPP/APLP2 family of Kunitz serine proteinase inhibitors regulate cerebral thrombosis.

PubMed

Xu, Feng; Previti, Mary Lou; Nieman, Marvin T; Davis, Judianne; Schmaier, Alvin H; Van Nostrand, William E

2009-04-29

The amyloid beta-protein precursor (AbetaPP) is best recognized as the precursor to the Abeta peptide that accumulates in the brains of patients with Alzheimer's disease, but less is known about its physiological functions. Isoforms of AbetaPP that contain a Kunitz-type serine proteinase inhibitor (KPI) domain are expressed in brain and, outside the CNS, in circulating blood platelets. Recently, we showed that KPI-containing forms of AbetaPP regulates cerebral thrombosis in vivo (Xu et al., 2005, 2007). Amyloid precursor like protein-2 (APLP2), a closely related homolog to AbetaPP, also possesses a highly conserved KPI domain. Virtually nothing is known of its function. Here, we show that APLP2 also regulates cerebral thrombosis risk. Recombinant purified KPI domains of AbetaPP and APLP2 both inhibit the plasma clotting in vitro. In a carotid artery thrombosis model, both AbetaPP(-/-) and APLP2(-/-) mice exhibit similar significantly shorter times to vessel occlusion compared with wild-type mice indicating a prothrombotic phenotype. Similarly, in an experimental model of intracerebral hemorrhage, both AbetaPP(-/-) and APLP2(-/-) mice produce significantly smaller hematomas with reduced brain hemoglobin content compared with wild-type mice. Together, these results indicate that AbetaPP and APLP2 share overlapping anticoagulant functions with regard to regulating thrombosis after cerebral vascular injury.

Mania triggered by sleep loss and risk of postpartum psychosis in women with bipolar disorder.

PubMed

Lewis, Katie J S; Di Florio, Arianna; Forty, Liz; Gordon-Smith, Katherine; Perry, Amy; Craddock, Nick; Jones, Lisa; Jones, Ian

2018-01-01

Women with bipolar disorder are at high risk of affective psychoses following childbirth (i.e. "postpartum psychosis", PP) and there is a need to identify which factors underlie this increased risk. Vulnerability to mood dysregulation following sleep loss may influence risk of PP, as childbirth is typified by sleep disruption. We investigated whether a history of mood episodes triggered by sleep loss was associated with PP in women with bipolar disorder (BD). Participants were 870 parous women with BD recruited to the Bipolar Disorder Research Network. Lifetime diagnoses of BD and perinatal episodes were identified via interview and case notes. Information on whether mood episodes had been triggered by sleep loss was derived at interview. Rates of PP were compared between women who did and did not report mood episodes following sleep loss. Women who reported sleep loss triggering episodes of mania were twice as likely to have experienced an episode of PP (OR = 2.09, 95% CI = 1.47-2.97, p < 0.001) compared to women who did not report this. There was no significant association between depression triggered by sleep loss and PP (p = 0.526). Data were cross-sectional therefore may be subject to recall bias. We also did not have objective data on sleep disruption that had occurred during the postpartum period or prior to mood episodes. In clinical practice, a history of mania following sleep loss could be a marker of increased vulnerability to PP, and should be discussed with BD women who are pregnant or planning to conceive. Copyright © 2017. Published by Elsevier B.V.

Effect of piperine on the bioavailability and pharmacokinetics of rosmarinic acid in rat plasma using UPLC-MS/MS.

PubMed

Yang, Jun-Hui; Mao, Kun-Jun; Huang, Ping; Ye, Yin-Jun; Guo, Hua-Shan; Cai, Bao-Chang

2018-02-01

1. The purpose of the present study was to investigate the effect of piperine (PP) on the pharmacokinetics of rosmarinic acid (RA) in rat plasma and to determine whether PP could enhance the oral bioavailability of RA via inhibition of its glucuronidation. 2. The pharmacokinetic profiles of RA between oral administration of RA (50 mg/kg) alone and in combination with different oral dose PP (20, 40, 60, and 80 mg/kg) to rats were investigated via a validated UPLC/MS/MS method. 3. The AUC and C max of RA were significantly increased in combination with different dose PP dose dependently, especially in the presence of 60 and 80 mg/kg PP (p < 0.01). The relative bioavailability of RA in the presence of 20, 40, 60, and 80 mg/kg PP was 1.24-, 1.32-, 2.02-, and 2.26-folds higher, respectively, compared with the control group given RA alone. Compared with RA, the pharmacokinetic modulations of RA glucuronide were even more apparent, and the glucuronidation of RA was remarkedly inhibited. 4. This study demonstrated that PP significantly improved the in vivo bioavailability of RA partly attributing to the inhibition of gut and hepatic metabolism enzymes of RA.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zissa, D.E.

The charged multiplicity cross sections of 50 GeV/c anti pp annihilation reactions are examined through the use of the corresponding anti pp - pp cross section differences. In addition, various four-constraint reactions such as the elastic reaction and the reaction anti pp ..-->.. anti pp ..pi../sup +/..pi../sup -/ are studied at the same incident anti p beam momentum. The source of the data is a film sample of 92,000 pictures of the 30-inch hydrogen bubble chamber exposed to an anti p enriched 50 GeV/c negative beam. There are 2.8 antiprotons per picture on the average. The proportional wire chambers allowmore » for precise measurement of beam and fast secondary charged particle trajectories. The average charged multiplicity of the difference distribution is larger than that of the anti pp sample as a whole. Although the anti pp - pp total cross section difference is approximately 12%, about 50% of the anti pp events with 14 charged particles appear in the difference. The difference distribution is in good agreement with a model by Eylon and Harari for anti pp annihilations. The model is based on simple counting rules for quark interaction diagrams. The form of the difference distribution has an energy dependence which may be interpreted as evidence for multiple cluster formation for anti pp annihilations above about 30 GeV. Alternatively, Koba-Nielsen-Olesen scaling describes the distribution over the entire range of existing data. Copius ..delta.. (1232) production and diffractive dissociation are exhibited in the reaction anti pp ..-->.. anti pp..pi../sup -/..pi../sup -/. The subchannel reaction anti pp ..-->.. anti ..delta../sup - -/..delta../sup - -/ is examined in terms of pion exchange. The cross sections for the reaction anti pp ..-->.. anti pp2..pi../sup -/2..pi../sup -/ is determined. No statistically significant amount of annihilation is found into two, four, and six charged pions without associated neutral particles.« less

An Analytical Model of Periodic Waves in Shallow Water--Summary.

DTIC Science & Technology

1984-01-01

Petviashvili equation , and is based on a Riemann theta function of genus 2. These bi-periodic waves are direct generalizations of the well-known (simply... Petviashvili (KP; 1970) equation , (ut 6uux + U ) 3uyy -0, (1) is a scaled, dimensionless equation that describes the evolution of long water waves of...Fluid Mech., vol. 92, pp 691-715 Dubrovin, B. A., 1981, Russ. Math. Surveys, vol. 36, pp 11-92 Kadomtsev , B. B. & V. I. Petviashvili , 1970,) Soy. Phys

Development and comparison of intramuscularly long-acting paliperidone palmitate nanosuspensions with different particle size.

PubMed

Leng, Donglei; Chen, Hongming; Li, Guangjing; Guo, Mengran; Zhu, Zhaolu; Xu, Lu; Wang, Yongjun

2014-09-10

The main purpose of this study was to develop and compare the pharmacokinetic behavior of two paliperidone palmitate (PP) nanosuspensions with different particle size after intramuscular (i.m.) administration. PP nanosuspensions were prepared by wet media milling method and the mean particle size of nanosuspension was controlled as 1,041 ± 6 nm (A) and 505 ± 9 nm (B), respectively. The morphology of nanosuspensions was observed by scanning electron microscope (SEM). Differential scanning calorimeter (DSC) and powder X-ray diffraction (PXRD) confirmed the crystallinity of PP in nanosuspensions. The physical and chemical stabilities of nanosuspensions A and B were investigated by particle analyzer and HPLC after storage for 2 months at 25°C, 4°C and mechanical shaking condition. No obvious change in particle size and chemical degradation of drug were observed. Following single-dose i.m. administration to beagle dogs, the release of paliperidone lasted for nearly 1 month. The Tmax of nanosuspensions A and B was 6 (d) and 10 (d). The AUC0-t and Cmax of nanosuspensions A was 2.0-fold and 1.8-fold higher than nanosuspensions B (p<0.05). The results demonstrated that PP nanosuspensions formulation had long-acting effect. Nanosuspension A with a larger particle size performed better than nanosuspension B. As a result, it is important to design appropriate particle size of nanosuspensions for i.m. administration in order to produce larger therapeutic effect. Copyright © 2014 Elsevier B.V. All rights reserved.

Effect of Placenta Previa on Preeclampsia

PubMed Central

Ying, Hao; Lu, Yi; Dong, Yi-Nuo; Wang, De-Fen

2016-01-01

Background The correlation between gestational hypertension-preeclampsia (GH-PE) and placenta previa (PP) is controversial. Specifically, it is unknown whether placenta previa has any effect on the various types of preeclampsia (PE), and the role PP with concurrent placenta accreta (PA) play in the occurrence of GH-PE are not well understood. Objective The aim of this study was to identify the effects of PP on GH, mild and severe preeclampsia (MPE and SPE), and early- and late-onset preeclampsia (EPE and LPE). Another aim of the study was to determine if concurrent PA impacts the relationship between PP and GH-PE. Methods A retrospective single-center study of 1,058 patients having singleton pregnancies with PP was performed, and 2,116 pregnant women were randomly included as controls. These cases were collected from a tertiary hospital and met the inclusion criteria for the study. Clinical information, including PP and the gestational age at the onset of GH-PE were collected. Binary and multiple logistic regression analyses were conducted after the confounding variables were controlled to assess the effects of PP on different types of GH-PE. Results There were 155 patients with GH-PE in the two groups. The incidences of GH-PE in the PP group and the control group were 2.5% (26/1058) and 6.1% (129/2116), respectively (P = 0.000). Binary and multiple regression analyses were conducted after controlling for confounding variables. Compared to the control group, in the PP group, the risk of GH-PE was reduced significantly by 78% (AOR: 0.216; 95% CI: 0.135–0.345); the risks of GH and PE were reduced by 55% (AOR: 0.451; 95% CI: 0.233–0.873) and 86% (AOR: 0.141; 95% CI: 0.073–0.271), respectively; the risks of MPE and SPE were reduced by 73% (AOR: 0.269; 95% CI: 0.087–0828) and 88% (AOR: 0.123; 95% CI: 0.055–0.279), respectively; and the risks of EPE and LPE were reduced by 95% (AOR: 0.047; 95% CI: 0.012–0.190) and 67% (AOR: 0.330; 95% CI: 0.153–0.715), respectively. The incidence of concurrent PA in women with PP was 5.86%; PP with PA did not significantly further reduce the incidence of GH-PE compared with PP without PA (1.64% vs. 2.51%, P>0.05). Binary logistic regression analyses were conducted after controlling for confounding variables, compared with the non-PP + GH-PE group, and the AOR of FGR in the non-PP + non-GH-PE group was 0.206 (0.124–0.342). Compared with the PP + GH-PE group, the AOR of FGR in the PP + non-GH-PE group was 0.430 (0.123–1.500). Conclusion PP is not only associated with a significant reduction in the incidence of GH-PE, but also is associated with a reduction in incidence of various types of PE. Concurrent PA and PP do not show association with a reduction in incidence of GH-PE. PMID:26731265

Spectroscopic investigations on the simulated solar light induced photodegradation of 4-nitrophenol by using three novel copper(II) porphyrin-TiO2 photocatalysts.

PubMed

Lü, Xiang-fei; Sun, Wan-jun; Li, Jun; Xu, Wei-xia; Zhang, Feng-xing

2013-07-01

Three porphyrins containing different functional groups (-OH, C-O2C2H5, -COOH), 5-(4-hydroxy) phenyl-10,15,20-triphenyl porphyrin (1a), 5-(4-ethylacetatatomethoxy) phenyl-10,15,20-triphenyl porphyrin (1b), 5-(4-carboxylatomethoxy) phenyl-10,15,20-triphenyl porphyrin (1c), were synthesized and characterized spectroscopically. The CuPp(2a, 2b, 2c)-TiO2 photocatalysts were then prepared and characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), UV-vis diffuse reflectance spectroscopy (UV-vis-DRS), Fourier-transform infrared spectroscopy (FT-IR). The photocatalytic activities of the photocatalysts were investigated by carrying out the photodegradation of 4-nitrophenol in aqueous solution under simulated solar irradiation. It was found that the CuPp(2a, 2b, 2c)-TiO2 enhanced the photocatalytic efficiency of bare TiO2 in photodegrading the 4-NP due to the interaction between CuPp(2a, 2b, 2c) and TiO2, resulted in the enhancement of the photogenerated electron-hole separation. The reasons of this enhanced photocatalytic activity were also discussed. Based on the present study, it could be considered as a promising photocatalyst for the further industrial application. Copyright © 2013 Elsevier B.V. All rights reserved.

PP2A regulates SCF-induced cardiac stem cell migration through interaction with p38 MAPK.

PubMed

Wang, Ying; Xia, Yanli; Kuang, Dong; Duan, Yaqi; Wang, Guoping

2017-12-15

Previous studies have shown that stem cell factor (SCF) induces the migration of cardiac stem cells (CSCs) and helps to repair myocardial infarctions. Earlier studies on the migration mechanism only focused on the activation of kinases; here, we aimed to explore the functional role of protein phosphatase 2A (PP2A) in SCF-induced CSC migration. CSCs were treated with SCF, PP2A enzymatic activity was measured, the phosphorylation levels of PP2A, p38 MAPK and cofilin were evaluated using western blot. Transwell assay was used to determine the migratory ability of CSCs. In vitro, SCF induced the phosphorylation of p38 MAPK and cofilin, leading to the migration of CSCs. Cofilin acted as a downstream signal of p38 MAPK. PP2A was involved in this process. Further studies revealed that PP2A was inactivated via phosphorylation at Tyr307 by SCF and the inactivation/phosphorylation was mediated by activated p38 MAPK, as p38 MAPK inhibitor SB203580 or siRNA prevented SCF-induced inactivation and phosphorylation of PP2A. When CSCs were pretreated with PP2A inhibitor (okadaic acid, OA), SCF-induced CSC migration and the downstream signals were enhanced, and the enhancement was reversed when p38 MAPK was blocked. Additionally, co-immunoprecipitation showed a direct interaction of PP2A with p38 MAPK. Our results indicated that PP2A regulated the SCF-induced activation of p38 MAPK/cofilin signaling pathway and subsequent migration of CSCs by interaction with p38 MAPK. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Downregulation of protein phosphatase 2A carboxyl methylation and methyltransferase may contribute to Alzheimer disease pathogenesis.

PubMed

Sontag, Estelle; Hladik, Christa; Montgomery, Lisa; Luangpirom, Ampa; Mudrak, Ingrid; Ogris, Egon; White, Charles L

2004-10-01

ABalphaC, a major protein phosphatase 2A (PP2A) heterotrimeric enzyme, binds to and regulates the microtubule cytoskeleton and tau. We have shown that ABalphaC protein expression levels are selectively reduced in Alzheimer disease (AD). Notably, the carboxyl methylation of PP2A catalytic subunit (PP2A(C)) is critically required for ABalphaC holoenzyme assembly, and catalyzed by a specific methyltransferase (PPMT). Here, we provide the first analysis of human PPMT and methylated PP2A(C) in brain regions from AD, non-AD demented, and aged control autopsy cases. Immunoblotting analyses revealed that PPMT protein expression and PP2A(C) methylation levels were quantitatively decreased in AD-affected brain regions. Immunohistochemical studies showed that PPMT was abundant in neurons throughout the cortex in normal control and non-AD demented cases. However, in AD, there was a regional loss of PPMT immunoreactivity that closely paralleled the severity of tau pathology, but not amyloid plaque burden. We propose that the deregulation of PPMT and PP2A methylation/demethylation cycles contributes to AD pathogenesis, by inducing changes in PP2A heteromultimeric composition and substrate specificity. In turn, PP2A dysfunction compromises the mechanisms that control tau, neuronal plasticity, and survival.

Effect of gamma radiation on the mechanical properties of natural silk fiber and synthetic E-glass fiber reinforced polypropylene composites: A comparative study

NASA Astrophysics Data System (ADS)

Shubhra, Quazi T. H.; Alam, A. K. M. M.

2011-11-01

Silk is a strong natural proteinous fiber and E-glass is a very strong synthetic fiber. Compression molding method was used to fabricate B. mori silk fiber reinforced polypropylene (PP) matrix composites. The tensile strength (TS), tensile modulus (TM), bending strength (BS), bending modulus (BM) and impact strength (IS) of prepared composites were 55.1 MPa, 780 MPa, 56.3 MPa, 3450 MPa and 17 kJ/m 2, respectively. Synthetic E-glass fiber reinforced PP based composites were fabricated in the same way and TS, TM, BS, BM, IS of E-glass fiber reinforced polypropylene composites were found to be 128.7 MPa, 4350 MPa, 141.6 MPa, 6300 MPa and 19 kJ/m 2, respectively. Gamma radiation is high energy ionizing radiation and was applied to increase the mechanical properties of the composites. Application of gamma ray increases the mechanical properties of silk/PP composites to a greater extent than that of E-glass/PP composites.

Developmental and light regulation of tumor suppressor protein PP2A in the retina

PubMed Central

Rajala, Ammaji; Wang, Yuhong; Abcouwer, Steven F.; Gardner, Thomas W.; Rajala, Raju V.S.

2018-01-01

Protein phosphatases are a group of universal enzymes that are responsible for the dephosphorylation of various proteins and enzymes in cells. Cellular signal transduction events are largely governed by the phosphorylation of key proteins. The length of cellular response depends on the activation of protein phosphatase that dephosphorylates the phosphate groups to halt a biological response, and fine-tune the defined cellular outcome. Dysregulation of these phosphatase(s) results in various disease phenotypes. The retina is a post-mitotic tissue, and oncogenic tyrosine and serine/ threonine kinase activities are important for retinal neuron survival. Aberrant activation of protein phosphatase(s) may have a negative effect on retinal neurons. In the current study, we characterized tumor suppressor protein phosphatase 2 (PP2A), a major serine/ threonine kinase with a broad substrate specificity. Our data suggest that PP2A is developmentally regulated in the retina, localized predominantly in the inner retina, and expressed in photoreceptor inner segments. Our findings indicate that PKCα and mTOR may serve as PP2A substrates. We found that light regulates PP2A activity. Our studies also suggest that rhodopsin regulates PP2A and its substrate(s) dephosphorylation. PP2A substrate phosphorylation is increased in mice lacking the A-subunit of PP2A. However, there is no accompanying effect on retina structure and function. Together, our findings suggest that controlling the activity of PP2A in the retina may be neuroprotective. PMID:29416710

Evidence for collective phenomena in pp collisions

NASA Astrophysics Data System (ADS)

Chen, Zhenyu; CMS Collaboration

2017-11-01

Measurements of two- and multi-particle angular correlations in pp collisions at √{ s} = 5, 7, and 13 TeV are presented. The data, corresponding to integrated luminosities of 1.0 pb-1 (5 TeV), 6.2 pb-1 (7 TeV), and 0.7 pb-1 (13 TeV), were collected using the CMS detector at the LHC. The second-order (v2) and third-order (v3) azimuthal anisotropy harmonics of unidentified charged particles, as well as v2 of Ks0 and Λ / Λ ‾ particles, are extracted from long-range two-particle correlations as functions of particle multiplicity and transverse momentum. For high-multiplicity pp events, a mass ordering is observed for the v2 values of charged hadrons (mostly pions), Ks0, and Λ / Λ ‾ at pT ≲ 2 GeV /c. The v2 signals are also extracted from four- and six-particle correlations for 13 TeV pp collisions, with comparable magnitude to those from two-particle correlations. These observations strongly support the interpretation of a collective origin for the observed long-range correlations in high-multiplicity pp collisions.

A novel transmembrane Ser/Thr kinase complexes with protein phosphatase-1 and inhibitor-2.

PubMed

Wang, Hong; Brautigan, David L

2002-12-20

Protein kinases and protein phosphatases exert coordinated control over many essential cellular processes. Here, we describe the cloning and characterization of a novel human transmembrane protein KPI-2 (Kinase/Phosphatase/Inhibitor-2) that was identified by yeast two-hybrid using protein phosphatase inhibitor-2 (Inh2) as bait. KPI-2 mRNA was predominantly expressed in skeletal muscle. KPI-2 is a 1503-residue protein with two predicted transmembrane helices at the N terminus, a kinase domain, followed by a C-terminal domain. The transmembrane helices were sufficient for targeting proteins to the membrane. KPI-2 kinase domain has about 60% identity with its closest relative, a tyrosine kinase. However, it only exhibited serine/threonine kinase activity in autophosphorylation reactions or with added substrates. KPI-2 kinase domain phosphorylated protein phosphatase-1 (PP1C) at Thr(320), which attenuated PP1C activity. KPI-2 C-terminal domain directly associated with PP1C, and this required a VTF motif. Inh2 associated with KPI-2 C-terminal domain with and without PP1C. Thus, KPI-2 is a kinase with sites to associate with PP1C and Inh2 to form a regulatory complex that is localized to membranes.

Prediction of maternal near-miss in placenta previa: a retrospective analysis from a tertiary center in Ankara, Turkey.

PubMed

Coskun, Bora; Akkurt, Iltac; Dur, Rıza; Akkurt, Mehmet O; Ergani, Seval Y; Turan, Ozerk T; Coskun, Bugra

2018-02-01

To determine risk factors for severe complications during and after cesarean delivery (CD) in placenta previa (PP). We reviewed retrospectively collected data from women with PP who underwent CD during a 6-year study period. We identified the complicated group based on the modified WHO near-miss criteria. Complicated and noncomplicated groups were compared considering clinical, laboratory, and sonographic features. Thirty-seven of 256 cases classified as near miss consisting of 14 peripartum hysterectomies, 12 uterine balloon placements, 10 great artery ligations, and four B-lynch suture placement procedures without maternal mortality. Perioperative complications included surgical wound infections (n = 5), bladder injury (n = 4), pelvic abscess (n = 1), and uterine rupture (n = 1). Logistic regression analyses demonstrated following features to be associated with maternal near miss in PP: (1) coexistent abruption (aOR 13.2, 95% CI 5.8-75.3), (2) morbidly adherent placenta (aOR 11.92, 95% CI 3.24-43.82), (3) number of hospitalizations for vaginal bleeding (≥3) (aOR 8.88, 95% CI 3.32-26.69), and (4) transvaginal cervical length (CL) measurement <10th percentile (aOR 5.5, 95% CI 2.1-15.4). Short cervical length, recurrent vaginal bleeding, morbidly adherent placenta, and concurrent placental abruption are independent predictors for subsequent severe maternal morbidity in PP cases. Early identification of these risk factors during PP follow-up may improve maternal outcome.

Sirolimus-coated, poly(L-lactic acid)-modified polypropylene mesh with minimal intra-peritoneal adhesion formation in a rat model.

PubMed

Lu, S; Hu, W; Zhang, Z; Ji, Z; Zhang, T

2018-05-18

This study evaluated the manufacturing method and anti-adhesion properties of a new composite mesh in the rat model, which was made from sirolimus (SRL) grafts on a poly(L-lactic acid) (PLLA)-modified polypropylene (PP) hernia mesh. PLLA was first grafted onto argon-plasma-treated native PP mesh through catalysis of stannous chloride. SRL was grafted onto the surface of PP-PLLA meshes using catalysis of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and 4-dimethylaminopyridine (DMAP) in a CH 2 Cl 2 solvent. Sprague-Dawley female rats received either SRL-coated meshes, PP-PLLA meshes, or native PP meshes to repair abdominal wall defects. At different intervals, rats were euthanized by a lethal dose of chloral hydrate and adhesion area and tenacity were evaluated. Sections of the mesh with adjacent tissues were assessed histologically. Attenuated total reflection Fourier transformed infrared (ATR-FTIR) spectroscopy indicated the existence of a C=O group absorption peak (1724.1 cm -1 ), and scanning electron microscope morphological analysis indicated that the surface of the PP mesh was covered with SRL. Compared to the native PP meshes and PP-PLLA meshes, SRL-coated meshes demonstrated the greatest ability to decrease the formation of adhesions (P < 0.05) and inflammation. The SRL-coated composite mesh showed minimal formation of intra-abdominal adhesions in a rat model of abdominal wall defect repair.

Observation of the decay B +→ψ(2S)Φ(1020)K + in pp collisions at s = 8 TeV

DOE PAGES

Khachatryan, Vardan

2017-01-10

Here, the decay B +→ψ(2S)Φ(1020)K + is observed for the first time using data collected from pp collisions at √s=8TeV by the CMS experiment at the LHC, corresponding to an integrated luminosity of 19.6 fb -1 . The branching fraction of this decay is measured, using the mode B +→ψ(2S)K + as normalization, to be (4.0±0.4(stat)±0.6(syst)±0.2(B))×10 -6, where the third uncertainty is from the measured branching fraction of the normalization channel.

Observation of the decay B +→ψ(2S)Φ(1020)K + in pp collisions at s = 8 TeV

DOE Office of Scientific and Technical Information (OSTI.GOV)

Khachatryan, Vardan

Here, the decay B +→ψ(2S)Φ(1020)K + is observed for the first time using data collected from pp collisions at √s=8TeV by the CMS experiment at the LHC, corresponding to an integrated luminosity of 19.6 fb -1 . The branching fraction of this decay is measured, using the mode B +→ψ(2S)K + as normalization, to be (4.0±0.4(stat)±0.6(syst)±0.2(B))×10 -6, where the third uncertainty is from the measured branching fraction of the normalization channel.

Highly sensitive detection and discrimination of LR and YR microcystins based on protein phosphatases and an artificial neural network.

PubMed

Covaci, O I; Sassolas, A; Alonso, G A; Muñoz, R; Radu, G L; Bucur, B; Marty, J-L

2012-08-01

The inhibition characteristics of three different protein phosphatases by three microcystin (MC) variants--LR, YR, and RR--were studied. The corresponding K (I) for each enzyme-MC couple was calculated. The toxicity of MC varies in the following order: MC-LR > MC-YR > MC-RR. The sensitivity of the enzymes increased in the following order: mutant PP2A < mutant PP1 < natural PP2A. The best limit of detection obtained was 21.2 pM MC-LR using the most sensible enzyme. Methanol, ethanol, and acetonitrile up to 2 % (v/v) may be used in inhibition measurements. An artificial neural network (ANN) was used to discriminate two MC variants--LR and YR--using the differences in inhibition percentages measured with mutant PP1 and natural PP2A. The ANN is able to analyze mixtures with concentrations ranging from 8 to 98 pM MC-LR and 31 to 373 pM MC-YR.

Modulation of the endogenous production of protoporphyrin IX in a yeast-based model organism

NASA Astrophysics Data System (ADS)

Joniová, Jaroslava; Gerelli, Emmanuel; Wagnières, Georges

2017-02-01

The main aim of this study was to assess conditions at which simple yeast-based model organism produces maximal levels of protoporphyrin IX (PpIX) after an exogenous administration of its precursor, 5-aminolevulinic acid (ALA), and the ferrous-ion chelator 2,2'-bipyridyl. We observed that the fluorescing porphyrin, produced after these administrations, was likely to be PpIX since fluorescence spectroscopy of the porphyrins produced endogenously in yeast cells resembles that of PpIX in DMSO and in vivo in the chick's chorioallantoic membrane model. Also, fluorescence lifetimes of these porphyrins are very similar to that of PpIX in vitro and in vivo. This suggests that PpIX is the main fluorescent compound produced by yeast in our conditions. We found that the conditions at which yeast produces the maximal PpIX were a synchronous administration of 5 μM ALA and 1 mM 2,2'-bipyridyl for yeast incubated in aqueous glucose and 1 mM 2,2'-bipyridyl in the presence of YPD medium. Such a simple model is of high interest to study basic mechanisms involved in the mitochondrial respiration since PpIX, which is produced in this organelle, can be used as an oxygen sensor, or to perform photodynamic therapy and photodiagnosis. Since the absorption and scattering coefficients of this model are much smaller than those of soft tissues over the visible part of the spectrum, a version of this model loaded with appropriated amounts of light absorbing and scattering particles could be designed as a phantom to mimic tumors containing PpIX, a useful tool to optimize certain cancer photodetection set-ups.

Crystallization and x-ray diffraction analysis of a putative bacterial class I labdane-related diterpene synthase [Crysallization and preliminary x-ray diffraction analysis of a bacterial class I labdane-related diterpene synthase

DOE PAGES

Serrano-Posada, Hugo; Centeno-Leija, Sara; Rojas-Trejo, Sonia; ...

2015-08-25

Here, labdane-related diterpenoids are natural products with potential pharmaceutical applications that are rarely found in bacteria. Here, a putative class I labdane-related diterpene synthase (LrdC) identified by genome mining in a streptomycete was successfully crystallized using the microbatch method. Crystals of the LrdC enzyme were obtained in a holo form with its natural cofactor Mg 2+ (LrdC-Mg 2+) and in complex with inorganic pyrophosphate (PP i) (LrdC-Mg 2+–PP i). Crystals of native LrdC-Mg 2+ diffracted to 2.50 Å resolution and belonged to the trigonal space group P3 221, with unit-cell parameters a = b = 107.1, c = 89.2 Å.more » Crystals of the LrdC-Mg 2+–PP i complex grown in the same conditions as the native enzyme with PEG 8000 diffracted to 2.36 Å resolution and also belonged to the trigonal space group P3 221. Crystals of the LrdC-Mg 2+–PP i complex grown in a second crystallization condition with PEG 3350 diffracted to 2.57 Å resolution and belonged to the monoclinic space group P2 1, with unit-cell parameters a = 49.9, b = 104.1, c = 66.5 Å, β = 111.4°. The structure was determined by the single-wavelength anomalous dispersion (SAD) technique using the osmium signal from a potassium hexachloroosmate (IV) derivative.« less

PP2A inhibition assay using recombinant enzyme for rapid detection of okadaic acid and its analogs in shellfish.

PubMed

Ikehara, Tsuyoshi; Imamura, Shihoko; Yoshino, Atsushi; Yasumoto, Takeshi

2010-01-01

Okadaic acid and its analogs (OAs) responsible for diarrhetic shellfish poisoning (DSP) strongly inhibit protein phosphatase 2A (PP2A) and thus are quantifiable by measuring the extent of the enzyme inhibition. In this study, we evaluated the suitability of the catalytic subunit of recombinant human PP2A (rhPP2Ac) for use in a microplate OA assay. OA, dinophysistoxin-1(DTX1), and hydrolyzate of 7-O-palmitoyl-OA strongly inhibited rhPP2Ac activity with IC(50) values of 0.095, 0.104, and 0.135 nM, respectively. The limits of detection and quantitation for OA in the digestive gland of scallops and mussels were 0.0348 μg/g and 0.0611 μg/g respectively, and, when converted to the whole meat basis, are well below the regulation level proposed by EU (0.16 μg/g whole meat). A good correlation with LC-MS data was demonstrated, the correlation coefficient being 0.996 with the regression slope of 1.097.

Antihelminthic drug niclosamide inhibits CIP2A and reactivates tumor suppressor protein phosphatase 2A in non-small cell lung cancer cells.

PubMed

Kim, Myeong-Ok; Choe, Min Ho; Yoon, Yi Na; Ahn, Jiyeon; Yoo, Minjin; Jung, Kwan-Young; An, Sungkwan; Hwang, Sang-Gu; Oh, Jeong Su; Kim, Jae-Sung

2017-11-15

Protein phosphatase 2A (PP2A) is a critical tumor suppressor complex responsible for the inactivation of various oncogenes. Recently, PP2A reactivation has emerged asan anticancer strategy. Cancerous inhibitor of protein phosphatase 2A (CIP2A), an endogenous inhibitor of PP2A, is upregulated in many cancer cells, including non-small cell lung cancer (NSCLC) cells. We demonstrated that the antihelminthic drug niclosamide inhibited the expression of CIP2A and reactivated the tumor suppressor PP2A in NSCLC cells. We performed a drug-repurposing screen and identified niclosamide asa CIP2A suppressor in NSCLC cells. Niclosamide inhibited cell proliferation, colony formation, and tumor sphere formation, and induced mitochondrial dysfunction through increased mitochondrial ROS production in NSCLC cells; however, these effects were rescued by CIP2A overexpression, which indicated that the antitumor activity of niclosamide was dependent on CIP2A. We found that niclosamide increased PP2A activity through CIP2A inhibition, which reduced the phosphorylation of several oncogenic proteins. Moreover, we found that a niclosamide analog inhibited CIP2A expression and increased PP2A activity in several types of NSCLC cells. Finally, we showed that other well-known PP2A activators, including forskolin and FTY720, did not inhibit CIP2A and that their activities were not dependent on CIP2A. Collectively, our data suggested that niclosamide effectively suppressed CIP2A expression and subsequently activated PP2A in NSCLC cells. This provided strong evidence for the potential use of niclosamide asa PP2A-activating drug in the clinical treatment of NSCLC. Copyright © 2017 Elsevier Inc. All rights reserved.

Phagosomal pH and glass fiber dissolution in cultured nasal epithelial cells and alveolar macrophages: a preliminary study.

PubMed Central

Johnson, N F

1994-01-01

The dissolution rate of glass fibers has been shown to be pH sensitive using in vitro lung fluid simulant models. The current study investigated whether there is a difference in phagosomal pH (ppH) between rat alveolar macrophages (AM) and rat nasal epithelial cells (RNEC) and whether such a difference would influence the dissolution of glass fibers. The ppH was measured in cultured AM and RNEC using flow cytometric, fluorescence-emission rationing techniques with fluorescein-labeled, amorphous silica particles. Glass fiber dissolution was determined in AM and RNEC cultured for 3 weeks with fast dissolving glass fibers (GF-A) or slow dissolving ones (GF-B). The mean diameters of GF-A were 2.7 microns and of GF-B, 2.6 microns, the average length of both fibers was approximately 22 to 25 microns. Dissolution was monitored by measuring the length and diameter of intracellular fibers and estimating the volume, assuming a cylindrical morphology. The ppH of AM was 5.2 to 5.8, and the ppH of RNEC was 7.0 to 7.5. The GF-A dissolved more slowly in RNEC than in AM, and no dissolution was evident in either cell type with GF-B. The volume loss with GF-A after a 3-week culture with AM was 66% compared to 45% for cultured RNEC. These results are different from those obtained using in vitro lung fluid-simulant models where dissolution is faster at higher pH. This difference suggests that dissolution rates of glass fibers in AM should not be applied to the dissolution of fibers in epithelial cells. Images Figure 1. a Figure 1. b Figure 2. a Figure 2. b Figure 3. a Figure 3. b PMID:7882965

Characterization of ppGalNAc-T18, a member of the vertebrate-specific Y subfamily of UDP-N-acetyl-α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferases.

PubMed

Li, Xing; Wang, Jing; Li, Wei; Xu, Yingjiao; Shao, Dong; Xie, Yinyin; Xie, Wenxian; Kubota, Tomomi; Narimatsu, Hisashi; Zhang, Yan

2012-05-01

The first step of mucin-type O-glycosylation is catalyzed by members of the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase (ppGalNAc-T; EC 2.4.1.41) family. Each member of this family has unique substrate specificity and expression profiles. In this report, we describe a new subfamily of ppGalNAc-Ts, designated the Y subfamily. The Y subfamily consists of four members, ppGalNAc-T8, -T9, -T17 and -T18, in which the conserved YDX(5)WGGENXE sequence in the Gal/GalNAc-T motif of ppGalNAc-Ts is mutated to LDX(5)YGGENXE. Phylogenetic analysis revealed that the Y subfamily members only exist in vertebrates. All four Y subfamily members lack in vitro GalNAc-transferase activity toward classical substrates possibly because of the UDP-GalNAc-binding pocket mutants. However, ppGalNAc-T18, the newly identified defining member, was localized in the endoplasmic reticulum rather than the Golgi apparatus in lung carcinoma cells. The knockdown of ppGalNAc-T18 altered cell morphology, proliferation potential and changed cell O-glycosylation. ppGalNAc-T18 can also modulate the in vitro GalNAc-transferase activity of ppGalNAc-T2 and -T10, suggesting that it may be a chaperone-like protein. These findings suggest that the new Y subfamily of ppGalNAc-Ts plays an important role in protein glycosylation; characterizing their functions will provide new insight into the role of ppGalNAc-Ts.

Study of prone positioning to reduce ventilator-associated pneumonia in hypoxaemic patients.

PubMed

Mounier, R; Adrie, C; Français, A; Garrouste-Orgeas, M; Cheval, C; Allaouchiche, B; Jamali, S; Dinh-Xuan, A T; Goldgran-Toledano, D; Cohen, Y; Azoulay, E; Timsit, J-F; Ricard, J-D

2010-04-01

The aim of the present study was to examine whether prone positioning (PP) affects ventilator associated-pneumonia (VAP) and mortality in patients with acute lung injury/adult respiratory distress syndrome. 2,409 prospectively included patients were admitted over 9 yrs (2000-2008) to 12 French intensive care units (ICUs) (OUTCOMEREA). The patients required invasive mechanical ventilation (MV) and had arterial oxygen tension/inspiratory oxygen fraction ratios <300 during the first 48 h. Controls were matched to PP patients on the PP propensity score (+/-10%), MV duration longer than that in PP patients before the first turn prone, and centre. VAP incidence was similar in the PP and control groups (24 versus 13 episodes.1,000 patient-days MV(-1) respectively, p = 0.14). After adjustment, PP did not decrease VAP occurrence (HR 1.64 (95% CI 0.70-3.84); p = 0.25) but significantly delayed hospital mortality (HR 0.56 (95% CI 0.39-0.79); p = 0.001), without decreasing 28-day mortality (37% in both groups). Post hoc analyses indicated that PP did not protect against VAP but, when used for >1 day, might decrease mortality and benefit the sickest patients (Simplified Acute Physiology Score >50). In ICU patients with hypoxaemic acute respiratory failure, PP had no effect on the risk of VAP. PP delayed mortality without decreasing 28-day mortality. PP >1 day might decrease mortality, particularly in the sickest patients.

Interleukin (IL)-8 immunoreactivity of injured axons and surrounding oligodendrocytes in traumatic head injury.

PubMed

Hayashi, Takahito; Ago, Kazutoshi; Nakamae, Takuma; Higo, Eri; Ogata, Mamoru

2016-06-01

Interleukin (IL)-8 has been suggested to be a positive regulator of myelination in the central nervous system, in addition to its principal role as a chemokine for neutrophils. Immunostaining for beta-amyloid precursor protein (AβPP) is an effective tool for detecting traumatic axonal injury, although AβPP immunoreactivity can also indicate axonal injury due to hypoxic causes. In this study, we examined IL-8 and AβPP immunoreactivity in sections of corpus callosum obtained from deceased patients with blunt head injury and from equivalent control tissue. AβPP immunoreactivity was detected in injured axons, such as axonal bulbs and varicose axons, in 24 of 44 head injury cases. These AβPP immunoreactive cases had survived for more than 3h. The AβPP immunostaining pattern can be classified into two types: traumatic (Pattern 1) and non-traumatic (Pattern 2) axonal injuries, which we described previously [Hayashi et al. Int. J. Legal Med. 129 (2015) 1085-1090]. Three of 44 control cases also showed AβPP immunoreactive injured axons as Pattern 2. In contrast, IL-8 immunoreactivity was detected in 7 AβPP immunoreactive and in 2 non-AβPP immunoreactive head injury cases, but was not detected in any of the 44 control cases, including the 3 AβPP immunoreactive control cases. The IL-8 immunoreactive cases had survived from 3 to 24 days, whereas those cases who survived less than 3 days (n=29) and who survived 90 days (n=1) were not IL-8 immunoreactive. Moreover, IL-8 was detected as Pattern 1 axons only. In addition, double immunofluorescence analysis showed that IL-8 is expressed by oligodendrocytes surrounding injured axons. In conclusion, our results suggest that immunohistochemical detection of IL-8 may be useful as a complementary diagnostic marker of traumatic axonal injury. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Atmospheric contamination by pesticides: Determination in the liquid, gaseous and particulate phases.

PubMed

Millet, M; Wortham, H; Sanusi, A; Mirabel, P

1997-01-01

Between 1991 and 1993, 18 fogwater samples, 31 rainwater samples and 17 atmosphere (gas and particles) samples were analysed for 13 pesticides (pp'DDT,pp'DDD,pp'DDE, aldrin, dieldrin, lindane, hexachlorobenzene, fenpropathrin, mecoprop, methyl-parathion, atrazine, isoproturon and aldicarb). The samples were collected in a rural area where some of the compounds are in use (experimental INRA farm, "Institut National de la Recherche Agronomique" in Colmar, Eastern France, 80,000 inhabitants). This paper briefly presents the analytical methodology used and, in detail, the contamination level of the different atmospheric phases. The contamination levels are roughly constant throughout the year in all the atmospheric phases and the most abundant pesticides are those commonly used on the experimental INRA farm and other surrounding farms. Nevertheless, some pesticides not used since the 1970s such as 1,1-Bis(4-chlorophenyl)-2,2,2-trichloroethane (pp'DDT) and 2,2-Bis(4-chlorophenyl)-1,1-dichloroethane (pp 'DDD) are also detected in the atmosphere of Colmar. A small increase in the pesticide concentrations in the atmosphere (gas and particles) was observed during treatments.

Plane-parallel waves as duals of the flat background III: T-duality with torsionless B-field

NASA Astrophysics Data System (ADS)

Hlavatý, Ladislav; Petr, Ivo; Petrásek, Filip

2018-04-01

By addition of non-zero, but torsionless B-field, we expand the classification of (non-)Abelian T-duals of the flat background in four dimensions with respect to 1, 2, 3 and 4D subgroups of the Poincaré group. We discuss the influence of the additional B-field on the process of dualization, and identify essential parts of the torsionless B-field that cannot in general be eliminated by coordinate or gauge transformation of the dual background. These effects are demonstrated using particular examples. Due to their physical importance, we focus on duals whose metrics represent plane-parallel (pp-)waves. Besides the previously found metrics, we find new pp-waves depending on parameters originating from the torsionless B-field. These pp-waves are brought into their standard forms in Brinkmann and Rosen coordinates.

Fasting and meal-induced CCK and PP secretion following intragastric balloon treatment for obesity.

PubMed

Mathus-Vliegen, Elisabeth M H; de Groot, Gerrit H

2013-05-01

Satiety is centrally and peripherally mediated by gastrointestinal peptides and the vagal nerve. We aimed to investigate whether intragastric balloon treatment affects satiety through effects on fasting and meal-stimulated cholecystokinin (CCK) and pancreatic polypeptide (PP) secretion. Patients referred for obesity treatment were randomised to 13 weeks of sham treatment followed by 13 weeks of balloon treatment (group 1; sham/balloon) or to twice a 13-week period of balloon treatment (group 2; balloon/balloon). Blood samples were taken for fasting and meal-stimulated CCK and PP levels at the start (T0) and after 13 (T1) and 26 (T2) weeks. Patients filled out visual analogue scales (VAS) to assess satiety. Forty-two patients (35 females, body weight 125.1 kg, BMI 43.3 kg/m(2)) participated. In group 1, basal CCK levels decreased but meal-stimulated response remained unchanged after 13 weeks of sham treatment. In group 2, basal and meal-stimulated CCK levels decreased after 13 weeks of balloon treatment. At the end of the second 13-week period, when group 1 had their first balloon treatment, they duplicated the initial 13-week results of group 2, whereas group 2 continued their balloon treatment and reduced meal-stimulated CCK release. Both groups showed reduced meal-stimulated PP secretions at T1 and T2 compared to T0. Changes in diet composition and VAS scores were similar. Improvements in glucose homeostasis partly explained the PP results. The reduced CCK and PP secretion after balloon positioning was unexpected and may reflect delayed gastric emptying induced by the balloon. Improved glucose metabolism partly explained the reduced PP secretion. Satiety and weight loss were not adversely influenced by these hormonal changes.

Direct and Indirect Targeting of PP2A by Conserved Bacterial Type-III Effector Proteins

PubMed Central

Jin, Lin; Ham, Jong Hyun; Hage, Rosemary; Zhao, Wanying; Soto-Hernández, Jaricelis; Lee, Sang Yeol; Paek, Seung-Mann; Kim, Min Gab; Boone, Charles; Coplin, David L.; Mackey, David

2016-01-01

Bacterial AvrE-family Type-III effector proteins (T3Es) contribute significantly to the virulence of plant-pathogenic species of Pseudomonas, Pantoea, Ralstonia, Erwinia, Dickeya and Pectobacterium, with hosts ranging from monocots to dicots. However, the mode of action of AvrE-family T3Es remains enigmatic, due in large part to their toxicity when expressed in plant or yeast cells. To search for targets of WtsE, an AvrE-family T3E from the maize pathogen Pantoea stewartii subsp. stewartii, we employed a yeast-two-hybrid screen with non-lethal fragments of WtsE and a synthetic genetic array with full-length WtsE. Together these screens indicate that WtsE targets maize protein phosphatase 2A (PP2A) heterotrimeric enzyme complexes via direct interaction with B’ regulatory subunits. AvrE1, another AvrE-family T3E from Pseudomonas syringae pv. tomato strain DC3000 (Pto DC3000), associates with specific PP2A B’ subunit proteins from its susceptible host Arabidopsis that are homologous to the maize B’ subunits shown to interact with WtsE. Additionally, AvrE1 was observed to associate with the WtsE-interacting maize proteins, indicating that PP2A B’ subunits are likely conserved targets of AvrE-family T3Es. Notably, the ability of AvrE1 to promote bacterial growth and/or suppress callose deposition was compromised in Arabidopsis plants with mutations of PP2A genes. Also, chemical inhibition of PP2A activity blocked the virulence activity of both WtsE and AvrE1 in planta. The function of HopM1, a Pto DC3000 T3E that is functionally redundant to AvrE1, was also impaired in specific PP2A mutant lines, although no direct interaction with B’ subunits was observed. These results indicate that sub-component specific PP2A complexes are targeted by bacterial T3Es, including direct targeting by members of the widely conserved AvrE-family. PMID:27191168

Reliability of Pseudotyped Influenza Viral Particles in Neutralizing Antibody Detection

PubMed Central

Yang, Jinghui; Li, Weidong; Long, Yunfeng; Song, Shaohui; Liu, Jing; Zhang, Xinwen; Wang, Xiaoguang; Jiang, Shude; Liao, Guoyang

2014-01-01

Background Current influenza control strategies require an active surveillance system. Pseudotyped viral particles (pp) together with the evaluation of pre-existing immunity in a population might satisfy this requirement. However, the reliability of using pp in neutralizing antibody (nAb) detection are undefined. Methodology/Principal Findings Pseudotyped particles of A(H1N1)pmd09 (A/California/7/2009) and HPAI H5N1 (A/Anhui/1/2005), as well as their reassortants, were generated. The reliability of using these pp in nAb detection were compared concurrently with the corresponding viruses by a hemagglutination inhibition test, as well as ELISA-, cytopathic effect-, and fluorescence-based microneutralization assays. In the qualitative detection on nAbs, the pp and their corresponding viruses were in complete agreement, with an R2 value equal to or near 1 in two different populations. In the quantitative detection on nAbs, although the geometric mean titers (95% confidence interval) differed between the pp and viruses, no significant difference was observed. Furthermore, humoral immunity against the reassortants was evaluated; our results indicated strong consistency between the nAbs against reassortant pp and those against naïve pp harboring the same hemagglutinin. Conclusion/Significance The pp displayed high reliability in influenza virus nAb detection. The use of reassortant pp is a safe and convenient strategy for characterizing emerging influenza viruses and surveying the disease burden. PMID:25436460

A First Cut at Doctrine for Automation of Division Command and Control.

DTIC Science & Technology

1985-12-02

34MSE: Mobile Subscriber Equipmentd," Arm-Y Communicator (Fall 1984), pp. 6-22. 20. Anthony L. Borelli and LTC Raymond J. Leopold, "Enhanced JTIDS: High...three, 1985. I’- pp. 85-8,. Berceau, CPT Stan. "ASAS." C2MUG Bulletin. September 1965, pp. 1-2. Borelli , Anthony L. and Leopold, LTC Raymond J

Measurement of sigma chi c2 B(chi c2-->J/psi gamma)/sigma chi c1 B(chi c1 -->J/psi gamma) in pp collisions at square root s=1.96 TeV.

PubMed

Abulencia, A; Adelman, J; Affolder, T; Akimoto, T; Albrow, M G; Ambrose, D; Amerio, S; Amidei, D; Anastassov, A; Anikeev, K; Annovi, A; Antos, J; Aoki, M; Apollinari, G; Arguin, J-F; Arisawa, T; Artikov, A; Ashmanskas, W; Attal, A; Azfar, F; Azzi-Bacchetta, P; Azzurri, P; Bacchetta, N; Badgett, W; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Baroiant, S; Bartsch, V; Bauer, G; Bedeschi, F; Behari, S; Belforte, S; Bellettini, G; Bellinger, J; Belloni, A; Benjamin, D; Beretvas, A; Beringer, J; Berry, T; Bhatti, A; Binkley, M; Bisello, D; Blair, R E; Blocker, C; Blumenfeld, B; Bocci, A; Bodek, A; Boisvert, V; Bolla, G; Bolshov, A; Bortoletto, D; Boudreau, J; Boveia, A; Brau, B; Brigliadori, L; Bromberg, C; Brubaker, E; Budagov, J; Budd, H S; Budd, S; Budroni, S; Burkett, K; Busetto, G; Bussey, P; Byrum, K L; Cabrera, S; Campanelli, M; Campbell, M; Canelli, F; Canepa, A; Carillo, S; Carlsmith, D; Carosi, R; Carron, S; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chang, S H; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, I; Cho, K; Chokheli, D; Chou, J P; Choudalakis, G; Chuang, S H; Chung, K; Chung, W H; Chung, Y S; Ciljak, M; Ciobanu, C I; Ciocci, M A; Clark, A; Clark, D; Coca, M; Compostella, G; Convery, M E; Conway, J; Cooper, B; Copic, K; Cordelli, M; Cortiana, G; Crescioli, F; Cuenca Almenar, C; Cuevas, J; Culbertson, R; Cully, J C; Cyr, D; DaRonco, S; Datta, M; D'Auria, S; Davies, T; D'Onofrio, M; Dagenhart, D; de Barbaro, P; De Cecco, S; Deisher, A; De Lentdecker, G; Dell'Orso, M; Delli Paoli, F; Demortier, L; Deng, J; Deninno, M; De Pedis, D; Derwent, P F; Di Giovanni, G P; Dionisi, C; Di Ruzza, B; Dittmann, J R; DiTuro, P; Dörr, C; Donati, S; Donega, M; Dong, P; Donini, J; Dorigo, T; Dube, S; Efron, J; Erbacher, R; Errede, D; Errede, S; Eusebi, R; Fang, H C; Farrington, S; Fedorko, I; Fedorko, W T; Feild, R G; Feindt, M; Fernandez, J P; Field, R; Flanagan, G; Foland, A; Forrester, S; Foster, G W; Franklin, M; Freeman, J C; Furic, I; Gallinaro, M; Galyardt, J; Garcia, J E; Garberson, F; Garfinkel, A F; Gay, C; Gerberich, H; Gerdes, D; Giagu, S; Giannetti, P; Gibson, A; Gibson, K; Gimmell, J L; Ginsburg, C; Giokaris, N; Giordani, M; Giromini, P; Giunta, M; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldschmidt, N; Goldstein, J; Golossanov, A; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gresele, A; Griffiths, M; Grinstein, S; Grosso-Pilcher, C; Group, R C; Grundler, U; Guimaraes da Costa, J; Gunay-Unalan, Z; Haber, C; Hahn, K; Hahn, S R; Halkiadakis, E; Hamilton, A; Han, B-Y; Han, J Y; Handler, R; Happacher, F; Hara, K; Hare, M; Harper, S; Harr, R F; Harris, R M; Hartz, M; Hatakeyama, K; Hauser, J; Heijboer, A; Heinemann, B; Heinrich, J; Henderson, C; Herndon, M; Heuser, J; Hidas, D; Hill, C S; Hirschbuehl, D; Hocker, A; Holloway, A; Hou, S; Houlden, M; Hsu, S-C; Huffman, B T; Hughes, R E; Husemann, U; Huston, J; Incandela, J; Introzzi, G; Iori, M; Ishizawa, Y; Ivanov, A; Iyutin, B; James, E; Jang, D; Jayatilaka, B; Jeans, D; Jensen, H; Jeon, E J; Jindariani, S; Jones, M; Joo, K K; Jun, S Y; Jung, J E; Junk, T R; Kamon, T; Karchin, P E; Kato, Y; Kemp, Y; Kephart, R; Kerzel, U; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kimura, N; Kirsch, L; Klimenko, S; Klute, M; Knuteson, B; Ko, B R; Kondo, K; Kong, D J; Konigsberg, J; Korytov, A; Kotwal, A V; Kovalev, A; Kraan, A C; Kraus, J; Kravchenko, I; Kreps, M; Kroll, J; Krumnack, N; Kruse, M; Krutelyov, V; Kubo, T; Kuhlmann, S E; Kuhr, T; Kusakabe, Y; Kwang, S; Laasanen, A T; Lai, S; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; Lazzizzera, I; LeCompte, T; Lee, J; Lee, J; Lee, Y J; Lee, S W; Lefèvre, R; Leonardo, N; Leone, S; Levy, S; Lewis, J D; Lin, C; Lin, C S; Lindgren, M; Lipeles, E; Lister, A; Litvintsev, D O; Liu, T; Lockyer, N S; Loginov, A; Loreti, M; Loverre, P; Lu, R-S; Lucchesi, D; Lujan, P; Lukens, P; Lungu, G; Lyons, L; Lys, J; Lysak, R; Lytken, E; Mack, P; MacQueen, D; Madrak, R; Maeshima, K; Makhoul, K; Maki, T; Maksimovic, P; Malde, S; Manca, G; Margaroli, F; Marginean, R; Marino, C; Marino, C P; Martin, A; Martin, M; Martin, V; Martínez, M; Maruyama, T; Mastrandrea, P; Masubuchi, T; Matsunaga, H; Mattson, M E; Mazini, R; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Menzemer, S; Menzione, A; Merkel, P; Mesropian, C; Messina, A; Miao, T; Miladinovic, N; Miles, J; Miller, R; Mills, C; Milnik, M; Mitra, A; Mitselmakher, G; Miyamoto, A; Moed, S; Moggi, N; Mohr, B; Moore, R; Morello, M; Movilla Fernandez, P; Mülmenstädt, J; Mukherjee, A; Muller, Th; Mumford, R; Murat, P; Nachtman, J; Nagano, A; Naganoma, J; Nakano, I; Napier, A; Necula, V; Neu, C; Neubauer, M S; Nielsen, J; Nigmanov, T; Nodulman, L; Norniella, O; Nurse, E; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Oldeman, R; Orava, R; Osterberg, K; Pagliarone, C; Palencia, E; Papadimitriou, V; Paramonov, A A; Parks, B; Pashapour, S; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Piedra, J; Pinera, L; Pitts, K; Plager, C; Pondrom, L; Portell, X; Poukhov, O; Pounder, N; Prakoshyn, F; Pronko, A; Proudfoot, J; Ptohos, F; Punzi, G; Pursley, J; Rademacker, J; Rahaman, A; Ranjan, N; Rappoccio, S; Reisert, B; Rekovic, V; Renton, P; Rescigno, M; Richter, S; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rogers, E; Rolli, S; Roser, R; Rossi, M; Rossin, R; Ruiz, A; Russ, J; Rusu, V; Saarikko, H; Sabik, S; Safonov, A; Sakumoto, W K; Salamanna, G; Saltó, O; Saltzberg, D; Sánchez, C; Santi, L; Sarkar, S; Sartori, L; Sato, K; Savard, P; Savoy-Navarro, A; Scheidle, T; Schlabach, P; Schmidt, E E; Schmidt, M P; Schmitt, M; Schwarz, T; Scodellaro, L; Scott, A L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semenov, A; Sexton-Kennedy, L; Sfyrla, A; Shapiro, M D; Shears, T; Shepard, P F; Sherman, D; Shimojima, M; Shochet, M; Shon, Y; Shreyber, I; Sidoti, A; Sinervo, P; Sisakyan, A; Sjolin, J; Slaughter, A J; Slaunwhite, J; Sliwa, K; Smith, J R; Snider, F D; Snihur, R; Soderberg, M; Soha, A; Somalwar, S; Sorin, V; Spalding, J; Spinella, F; Spreitzer, T; Squillacioti, P; Stanitzki, M; Staveris-Polykalas, A; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Stuart, D; Suh, J S; Sukhanov, A; Sun, H; Suzuki, T; Taffard, A; Takashima, R; Takeuchi, Y; Takikawa, K; Tanaka, M; Tanaka, R; Tecchio, M; Teng, P K; Terashi, K; Thom, J; Thompson, A S; Thomson, E; Tipton, P; Tiwari, V; Tkaczyk, S; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Tourneur, S; Trischuk, W; Tsuchiya, R; Tsuno, S; Turini, N; Ukegawa, F; Unverhau, T; Uozumi, S; Usynin, D; Vallecorsa, S; van Remortel, N; Varganov, A; Vataga, E; Vázquez, F; Velev, G; Veramendi, G; Veszpremi, V; Vidal, R; Vila, I; Vilar, R; Vine, T; Vollrath, I; Volobouev, I; Volpi, G; Würthwein, F; Wagner, P; Wagner, R G; Wagner, R L; Wagner, J; Wagner, W; Wallny, R; Wang, S M; Warburton, A; Waschke, S; Waters, D; Weinberger, M; Wester, W C; Whitehouse, B; Whiteson, D; Wicklund, A B; Wicklund, E; Williams, G; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, C; Wright, T; Wu, X; Wynne, S M; Yagil, A; Yamamoto, K; Yamaoka, J; Yamashita, T; Yang, C; Yang, U K; Yang, Y C; Yao, W M; Yeh, G P; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanello, L; Zanetti, A; Zaw, I; Zhang, X; Zhou, J; Zucchelli, S

2007-06-08

We measure the ratio of cross section times branching fraction, Rp=sigma chi c2 B(chi c2-->J/psi gamma)/sigma chi c1 B(chi c1-->J/psi gamma), in 1.1 fb(-1) of pp collisions at square root s=1.96 TeV. This measurement covers the kinematic range pT(J/psi)>4.0 GeV/c, |eta(J/psi)<1.0, and pT(gamma)>1.0 GeV/c. For events due to prompt processes, we find Rp=0.395+/-0.016(stat)+/-0.015(syst). This result represents a significant improvement in precision over previous measurements of prompt chi c1,2 hadro production.

Stimulation of the cardiac myocyte Na+-K+ pump due to reversal of its constitutive oxidative inhibition

PubMed Central

Chia, Karin K. M.; Liu, Chia-Chi; Hamilton, Elisha J.; Garcia, Alvaro; Fry, Natasha A.; Hannam, William; Figtree, Gemma A.

2015-01-01

Protein kinase C can activate NADPH oxidase and induce glutathionylation of the β1-Na+-K+ pump subunit, inhibiting activity of the catalytic α-subunit. To examine if signaling of nitric oxide-induced soluble guanylyl cyclase (sGC)/cGMP/protein kinase G can cause Na+-K+ pump stimulation by counteracting PKC/NADPH oxidase-dependent inhibition, cardiac myocytes were exposed to ANG II to activate NADPH oxidase and inhibit Na+-K+ pump current (Ip). Coexposure to 3-(5′-hydroxymethyl-2′-furyl)-1-benzylindazole (YC-1) to stimulate sGC prevented the decrease of Ip. Prevention of the decrease was abolished by inhibition of protein phosphatases (PP) 2A but not by inhibition of PP1, and it was reproduced by an activator of PP2A. Consistent with a reciprocal relationship between β1-Na+-K+ pump subunit glutathionylation and pump activity, YC-1 decreased ANG II-induced β1-subunit glutathionylation. The decrease induced by YC-1 was abolished by a PP2A inhibitor. YC-1 decreased phosphorylation of the cytosolic p47phox NADPH oxidase subunit and its coimmunoprecipitation with the membranous p22phox subunit, and it decreased O2·−-sensitive dihydroethidium fluorescence of myocytes. Addition of recombinant PP2A to myocyte lysate decreased phosphorylation of p47phox indicating the subunit could be a substrate for PP2A. The effects of YC-1 to decrease coimmunoprecipitation of p22phox and p47phox NADPH oxidase subunits and decrease β1-Na+-K+ pump subunit glutathionylation were reproduced by activation of nitric oxide-dependent receptor signaling. We conclude that sGC activation in cardiac myocytes causes a PP2A-dependent decrease in NADPH oxidase activity and a decrease in β1 pump subunit glutathionylation. This could account for pump stimulation with neurohormonal oxidative stress expected in vivo. PMID:26084308

Measurement of the Υ ( 1 S ) , Υ ( 2 S ) , and Υ ( 3 S ) cross sections in pp collisions at s = 7   TeV

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chatrchyan, S.; Khachatryan, V.; Sirunyan, A. M.

Themore » $$\\Upsilon$$(1S), $$\\Upsilon$$(2S), and $$\\Upsilon$$(3S) production cross sections are measured using a data sample corresponding to an integrated luminosity of 35.8 $$\\pm$$ 1.4 inverse picobarns of proton-proton collisions at $$\\sqrt{s}$$ = 7 TeV, collected with the CMS detector at the LHC. Upsilon resonances are identified through their decays to dimuons. Integrated over the $$\\Upsilon$$ transverse momentum range $$p_{t}^{\\Upsilon} \\lt$$ 50GeV and rapidity range |$$y^\\Upsilon$$| $$\\lt$$ 2.4, and assuming unpolarized Upsilon production, the products of the Upsilon production cross sections and dimuon branching fractions are \\begin{equation*}\\sigma(pp \\to \\Upsilon(1S) X) . B(\\Upsilon(1S) \\to \\mu^+ \\mu^-) = (8.55 \\pm 0.05^{+0.56}_{-0.50} \\pm 0.34) nb,\\end{equation*} \\begin{equation*}\\sigma(pp \\to \\Upsilon(2S) X) . B(\\Upsilon(2S) \\to \\mu^+ \\mu^-) = (2.21 \\pm 0.03^{+0.16}_{-0.14} \\pm 0.09) nb,\\end{equation*} \\begin{equation*}\\sigma(pp \\to \\Upsilon(3S) X) . B(\\Upsilon(3S) \\to \\mu^+ \\mu^-) = (1.11 \\pm 0.02^{+0.10}_{-0.08} \\pm 0.04) nb, \\end{equation*} where the first uncertainty is statistical, the second is systematic, and the third is from the uncertainty in the integrated luminosity. differential cross sections in bins of transverse momentum and rapidity, and the cross section ratios are presented. Cross section measurements performed within a restricted muon kinematic range and not corrected for acceptance are also provided. These latter measurements are independent of Upsilon polarization assumptions. results are compared to theoretical predictions and previous measurements.« less

Sds22 regulates aurora B activity and microtubule–kinetochore interactions at mitosis

PubMed Central

Posch, Markus; Khoudoli, Guennadi A.; Swift, Sam; King, Emma M.; DeLuca, Jennifer G.

2010-01-01

We have studied Sds22, a conserved regulator of protein phosphatase 1 (PP1) activity, and determined its role in modulating the activity of aurora B kinase and kinetochore–microtubule interactions. Sds22 is required for proper progression through mitosis and localization of PP1 to mitotic kinetochores. Depletion of Sds22 increases aurora B T-loop phosphorylation and the rate of recovery from monastrol arrest. Phospho–aurora B accumulates at kinetochores in Sds22-depleted cells juxtaposed to critical kinetochore substrates. Sds22 modulates sister kinetochore distance and the interaction between Hec1 and the microtubule lattice and, thus, the activation of the spindle assembly checkpoint. These results demonstrate that Sds22 specifically defines PP1 function and localization in mitosis. Sds22 regulates PP1 targeting to the kinetochore, accumulation of phospho–aurora B, and force generation at the kinetochore–microtubule interface. PMID:20921135

Development of the Radiation Stabilized Distributed Flux Burner. Phase 1, final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sullivan, J.D.; Duret, M.J.

1997-06-01

The RSB was first developed for Thermally Enhanced Oil Recovery steamers which fire with a single 60 MMBtu/hr burner; the California Energy Commission and Chevron USA were involved in the burner development. The burner has also since found applications in refinery and chemical plant process heaters. All Phase I goals were successfully met: the RSB achieved sub-9 ppM NOx and sub-50 ppM CO emissions using high excess air, external flue gas recirculation (FGR), and fuel staging in the 3 MMBtu/hr laboratory watertube boiler. In a test in a 50,000 lb/hr oil field steamer with fuel staging, it consistently achieved sub-20more » ppM NOx and as low as 10 ppM NOx. With high CO{sub 2} casing gas in this steamer, simulating external FGR, sub-20 ppM NOx and as low as 5 ppM NOx were achieved. Burner material cost was reduced by 25% on a per Btu basis by increasing the effective surface firing rate at the burner; further reductions will occur in Phase II. The market for 30 ppM and 9 ppM low NOx burners has been identified as package boilers in the 50,000 to 250,000 lb/hr size range (the 30 ppM is for retrofit, the 9 ppM for the new boiler market). Alzeta and Babcock & Wilcox have teamed to sell both boiler retrofits and new boilers; they have identified boiler designs which use the compact flame shape of the RSB and can increase steam capacity while maintaining the same boiler footprint. Alzeta, Chevron, and B & W have teamed to identify sites to demonstrate the RSB in Phases II and III. In Phase II, the RSB will be demonstrated in a 100,000 lb/hr industrial watertube boiler.« less

A Dynamic Analysis of Piezoelectric Strained Elements.

DTIC Science & Technology

1992-12-01

Type Quartz Crystal Plates ", IEEE SU- 29 (3), pp. 1 2 1 - 1 2 7 (1982). [107] L.K.Chau,High -frequency Long-wave Vibrations of Piezoelectric Ceramic ... Plate Excited with Voltage", Acta Acustica, 8 (5), pp. 300-310 (1983). [265] M.Ting-rong, "Forced Vibrations of Metal-Piezo- ceramic Thin Composite... ceramic and Metal Composite Thin Circular Plate with Different Diameter for Each Layer", Acta Acustica, 9 (5), pp. 298-310 (1984); Chinese J. Acoust., 2(3

An extract of Urtica dioica L. mitigates obesity induced insulin resistance in mice skeletal muscle via protein phosphatase 2A (PP2A).

PubMed

Obanda, Diana N; Ribnicky, David; Yu, Yongmei; Stephens, Jacqueline; Cefalu, William T

2016-02-26

The leaf extract of Urtica dioica L. (UT) has been reported to improve glucose homeostasis in vivo, but definitive studies on efficacy and mechanism of action are lacking. We investigated the effects of UT on obesity- induced insulin resistance in skeletal muscle. Male C57BL/6J mice were divided into three groups: low-fat diet (LFD), high-fat diet (HFD) and HFD supplemented with UT. Body weight, body composition, plasma glucose and plasma insulin were monitored. Skeletal muscle (gastrocnemius) was analyzed for insulin sensitivity, ceramide accumulation and the post translational modification and activity of protein phosphatase 2A (PP2A). PP2A is activated by ceramides and dephosphorylates Akt. C2C12 myotubes exposed to excess free fatty acids with or without UT were also evaluated for insulin signaling and modulation of PP2A. The HFD induced insulin resistance, increased fasting plasma glucose, enhanced ceramide accumulation and PP2A activity in skeletal muscle. Supplementation with UT improved plasma glucose homeostasis and enhanced skeletal muscle insulin sensitivity without affecting body weight and body composition. In myotubes, UT attenuated the ability of FFAs to induce insulin resistance and PP2A hyperactivity without affecting ceramide accumulation and PP2A expression. UT decreased PP2A activity through posttranslational modification that was accompanied by a reduction in Akt dephosphorylation.

Heme Oxygenase-1 Induction Improves Cardiac Function following Myocardial Ischemia by Reducing Oxidative Stress

PubMed Central

Issan, Yossi; Kornowski, Ran; Aravot, Dan; Shainberg, Asher; Laniado-Schwartzman, Michal; Sodhi, Komal; Abraham, Nader G.; Hochhauser, Edith

2014-01-01

Background Oxidative stress plays a key role in exacerbating diabetes and cardiovascular disease. Heme oxygenase-1 (HO-1), a stress response protein, is cytoprotective, but its role in post myocardial infarction (MI) and diabetes is not fully characterized. We aimed to investigate the protection and the mechanisms of HO-1 induction in cardiomyocytes subjected to hypoxia and in diabetic mice subjected to LAD ligation. Methods In vitro: cultured cardiomyocytes were treated with cobalt-protoporphyrin (CoPP) and tin protoporphyrin (SnPP) prior to hypoxic stress. In vivo: CoPP treated streptozotocin-induced diabetic mice were subjected to LAD ligation for 2/24 h. Cardiac function, histology, biochemical damage markers and signaling pathways were measured. Results HO-1 induction lowered release of lactate dehydrogenase (LDH) and creatine phospho kinase (CK), decreased propidium iodide staining, improved cell morphology and preserved mitochondrial membrane potential in cardiomyocytes. In diabetic mice, Fractional Shortening (FS) was lower than non-diabetic mice (35±1%vs.41±2, respectively p<0.05). CoPP-treated diabetic animals improved cardiac function (43±2% p<0.01), reduced CK, Troponin T levels and infarct size compared to non-treated diabetic mice (P<0.01, P<0.001, P<0.01 respectively). CoPP-enhanced HO-1 protein levels and reduced oxidative stress in diabetic animals, as indicated by the decrease in superoxide levels in cardiac tissues and plasma TNFα levels (p<0.05). The increased levels of HO-1 by CoPP treatment after LAD ligation led to a shift of the Bcl-2/bax ratio towards the antiapoptotic process (p<0.05). CoPP significantly increased the expression levels of pAKT and pGSK3β (p<0.05) in cardiomyocytes and in diabetic mice with MI. SnPP abolished CoPP's cardioprotective effects. Conclusions HO-1 induction plays a role in cardioprotection against hypoxic damage in cardiomyocytes and in reducing post ischemic cardiac damage in the diabetic heart as proved by the increased levels of pAKT with a concomitant inhibition of pGSK3β leading to preserved mitochondrial membrane potential. PMID:24658657

Phosphorylation of PP1 Regulator Sds22 by PLK1 Ensures Accurate Chromosome Segregation.

PubMed

Duan, Hequan; Wang, Chunli; Wang, Ming; Gao, Xinjiao; Yan, Maomao; Akram, Saima; Peng, Wei; Zou, Hanfa; Wang, Dong; Zhou, Jiajia; Chu, Youjun; Dou, Zhen; Barrett, Gregory; Green, Hadiyah-Nichole; Wang, Fangjun; Tian, Ruijun; He, Ping; Wang, Wenwen; Liu, Xing; Yao, Xuebiao

2016-09-30

During cell division, accurate chromosome segregation is tightly regulated by Polo-like kinase 1 (PLK1) and opposing activities of Aurora B kinase and protein phosphatase 1 (PP1). However, the regulatory mechanisms underlying the aforementioned hierarchical signaling cascade during mitotic chromosome segregation have remained elusive. Sds22 is a conserved regulator of PP1 activity, but how it regulates PP1 activity in space and time during mitosis remains elusive. Here we show that Sds22 is a novel and cognate substrate of PLK1 in mitosis, and the phosphorylation of Sds22 by PLK1 elicited an inhibition of PP1-mediated dephosphorylation of Aurora B at threonine 232 (Thr 232 ) in a dose-dependent manner. Overexpression of a phosphomimetic mutant of Sds22 causes a dramatic increase in mitotic delay, whereas overexpression of a non-phosphorylatable mutant of Sds22 results in mitotic arrest. Mechanistically, the phosphorylation of Sds22 by PLK1 strengthens the binding of Sds22 to PP1 and inhibits the dephosphorylation of Thr 232 of Aurora B to ensure a robust, error-free metaphase-anaphase transition. These findings delineate a conserved signaling hierarchy that orchestrates dynamic protein phosphorylation and dephosphorylation of critical mitotic regulators during chromosome segregation to guard chromosome stability. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Protein phosphatase 2A mediates JS-K-induced apoptosis by affecting Bcl-2 family proteins in human hepatocellular carcinoma HepG2 cells.

PubMed

Liu, Ling; Huang, Zile; Chen, Jingjing; Wang, Jiangang; Wang, Shuying

2018-04-25

Protein phosphatase 2A (PP2A) is an important enzyme within various signal transduction pathways. The present study was investigated PP2A mediates JS-K-induced apoptosis by affecting Bcl-2 family protein. JS-K showed diverse inhibitory effects in five HCC cell lines, especially HepG2 cells. JS-K caused a dose- and time-dependent reduction in cell viability and increased in levels of LDH release. Meanwhile, JS-K- induced apoptosis was characterized by mitochondrial membrane potential reduction, Hoechst 33342 + /PI + dual staining, release of cytochrome c (Cyt c), and activation of cleaved caspase-9/3. Moreover, JS-K-treatment could lead to the activation of protein phosphatase 2A-C (PP2A-C), decrease of anti-apoptotic Bcl-2 family-protein expression including p-Bcl-2 (Ser70), Bcl-2, Bcl-xL, and Mcl-1 as well as the increase of pro-apoptosis Bcl-2 family-protein including Bim, Bad, Bax, and Bak. Furthermore, JS-K caused a marked increase of intracellular NO levels while pre-treatment with Carboxy-PTIO (a NO scavenger) reduced the cytotoxicity effects and the apoptosis rate. Meanwhile, pre-treatment with Carboxy-PTIO attenuated the JS-K-induced up-regulation of PP2A, Cyt c, and cleaved-caspase-9/3 activation. The silencing PP2A-C by siRNA could abolish the activation of PP2A-C, down-regulation of anti-apoptotic Bcl-2 family-protein (p-Bcl-2, Bcl-2, Bcl-xL, and Mcl-1), increase of pro-apoptosis Bcl-2 family-protein (Bim, Bad, Bax, and Bak) and apoptotic-related protein (Cyt c, cleaved caspase-9/3) that were caused by JS-K in HepG2 cells. In addition, pre-treatment with OA (a PP2A inhibitor) also attenuated the above effects induced by JS-K. In summary, NO release from JS-K induces apoptosis through PP2A activation, which contributed to the regulation of Bcl-2 family proteins. © 2018 Wiley Periodicals, Inc.

Morphology and crystalline-phase-dependent electrical insulating properties in tailored polypropylene for HVDC cables

NASA Astrophysics Data System (ADS)

Zha, Jun-Wei; Yan, Hong-Da; Li, Wei-Kang; Dang, Zhi-Min

2016-11-01

Polypropylene (PP) has become one promising material to potentially replace the cross-link polyethylene used for high voltage direct current cables. Besides the isotactic polypropylene, the block polypropylene (b-PP) and random polypropylene (r-PP) can be synthesized through the copolymerization of ethylene and propylene molecules. In this letter, the effect of morphology and crystalline phases on the insulating electrical properties of PP was investigated. It was found that the introduction of polyethylene monomer resulted in the formation of β and γ phases in b-PP and r-PP. The results from the characteristic trap energy levels indicated that the β and γ phases could induce deep electron traps which enable to capture the carriers. And the space charge accumulation was obviously suppressed. Besides, the decreased electrical conductivity was observed in b-PP and r-PP. It is attributed to the existence of deep traps which can effectively reduce the carrier mobility and density in materials.

ARPP-16 Is a Striatal-Enriched Inhibitor of Protein Phosphatase 2A Regulated by Microtubule-Associated Serine/Threonine Kinase 3 (Mast 3 Kinase)

PubMed Central

Andrade, Erika C.; Musante, Veronica; Horiuchi, Atsuko; Greengard, Paul; Taylor, Jane R.

2017-01-01

ARPP-16 (cAMP-regulated phospho-protein of molecular weight 16 kDa) is one of several small acid-soluble proteins highly expressed in medium spiny neurons of striatum that are phosphorylated in response to dopamine acting via D1 receptor/protein kinase A (PKA) signaling. We show here that ARPP-16 is also phosphorylated in vitro and in vivo by microtubule-associated serine/threonine kinase 3 (MAST3 kinase), an enzyme of previously unknown function that is enriched in striatum. We find that ARPP-16 interacts directly with the scaffolding A subunit of the serine/threonine protein phosphatase, PP2A, and that phosphorylation of ARPP-16 at Ser46 by MAST3 kinase converts the protein into a selective inhibitor of B55α- and B56δ-containing heterotrimeric forms of PP2A. Ser46 of ARPP-16 is phosphorylated to a high basal stoichiometry in striatum, suggestive of basal inhibition of PP2A in striatal neurons. In support of this hypothesis, conditional knock-out of ARPP-16 in CaMKIIα::cre/floxed ARPP-16/19 mice results in dephosphorylation of a subset of PP2A substrates including phospho-Thr75-DARPP-32, phospho-T308-Akt, and phospho-T202/Y204-ERK. Conditional knock-out of ARPP-16/19 is associated with increased motivation measured on a progressive ratio schedule of food reinforcement, yet an attenuated locomotor response to acute cocaine. Our previous studies have shown that ARPP-16 is phosphorylated at Ser88 by PKA. Activation of PKA in striatal slices leads to phosphorylation of Ser88, and this is accompanied by marked dephosphorylation of Ser46. Together, these studies suggest that phospho-Ser46-ARPP-16 acts to basally control PP2A in striatal medium spiny neurons but that dopamine acting via PKA inactivates ARPP-16 leading to selective potentiation of PP2A signaling. SIGNIFICANCE STATEMENT We describe a novel mechanism of signal transduction enriched in medium spiny neurons of striatum that likely mediates effects of the neurotransmitter dopamine acting on these cells. We find that the protein ARPP-16, which is highly expressed in striatal medium spiny neurons, acts as a selective inhibitor of certain forms of the serine/threonine protein phosphatase, PP2A, when phosphorylated by the kinase, MAST3. Under basal conditions, ARPP-16 is phosphorylated by MAST3 to a very high stoichiometry. However, the actions of MAST3 are antagonized by dopamine and cAMP-regulated signaling leading to disinhibition of ARPP-16 and increased PP2A action. PMID:28167675

ARPP-16 Is a Striatal-Enriched Inhibitor of Protein Phosphatase 2A Regulated by Microtubule-Associated Serine/Threonine Kinase 3 (Mast 3 Kinase).

PubMed

Andrade, Erika C; Musante, Veronica; Horiuchi, Atsuko; Matsuzaki, Hideo; Brody, A Harrison; Wu, Terence; Greengard, Paul; Taylor, Jane R; Nairn, Angus C

2017-03-08

ARPP-16 (cAMP-regulated phospho-protein of molecular weight 16 kDa) is one of several small acid-soluble proteins highly expressed in medium spiny neurons of striatum that are phosphorylated in response to dopamine acting via D1 receptor/protein kinase A (PKA) signaling. We show here that ARPP-16 is also phosphorylated in vitro and in vivo by microtubule-associated serine/threonine kinase 3 (MAST3 kinase), an enzyme of previously unknown function that is enriched in striatum. We find that ARPP-16 interacts directly with the scaffolding A subunit of the serine/threonine protein phosphatase, PP2A, and that phosphorylation of ARPP-16 at Ser46 by MAST3 kinase converts the protein into a selective inhibitor of B55α- and B56δ-containing heterotrimeric forms of PP2A. Ser46 of ARPP-16 is phosphorylated to a high basal stoichiometry in striatum, suggestive of basal inhibition of PP2A in striatal neurons. In support of this hypothesis, conditional knock-out of ARPP-16 in CaMKIIα::cre/floxed ARPP-16/19 mice results in dephosphorylation of a subset of PP2A substrates including phospho-Thr75-DARPP-32, phospho-T308-Akt, and phospho-T202/Y204-ERK. Conditional knock-out of ARPP-16/19 is associated with increased motivation measured on a progressive ratio schedule of food reinforcement, yet an attenuated locomotor response to acute cocaine. Our previous studies have shown that ARPP-16 is phosphorylated at Ser88 by PKA. Activation of PKA in striatal slices leads to phosphorylation of Ser88, and this is accompanied by marked dephosphorylation of Ser46. Together, these studies suggest that phospho-Ser46-ARPP-16 acts to basally control PP2A in striatal medium spiny neurons but that dopamine acting via PKA inactivates ARPP-16 leading to selective potentiation of PP2A signaling. SIGNIFICANCE STATEMENT We describe a novel mechanism of signal transduction enriched in medium spiny neurons of striatum that likely mediates effects of the neurotransmitter dopamine acting on these cells. We find that the protein ARPP-16, which is highly expressed in striatal medium spiny neurons, acts as a selective inhibitor of certain forms of the serine/threonine protein phosphatase, PP2A, when phosphorylated by the kinase, MAST3. Under basal conditions, ARPP-16 is phosphorylated by MAST3 to a very high stoichiometry. However, the actions of MAST3 are antagonized by dopamine and cAMP-regulated signaling leading to disinhibition of ARPP-16 and increased PP2A action. Copyright © 2017 the authors 0270-6474/17/372709-14$15.00/0.

Measurements of inclusive W and Z cross sections in pp collisions at sqrt(s)=7 TeV

DOE Office of Scientific and Technical Information (OSTI.GOV)

Khachatryan, V.; et al.,

2011-01-01

Measurements of inclusive W and Z boson production cross sections in pp collisions at sqrt(s)=7 TeV are presented, based on 2.9 inverse picobarns of data recorded by the CMS detector at the LHC. The measurements, performed in the electron and muon decay channels, are combined to give sigma(pp to WX) times B(W to muon or electron + neutrino) = 9.95 \\pm 0.07(stat.) \\pm 0.28(syst.) \\pm 1.09(lumi.) nb and sigma(pp to ZX) times B(Z to oppositely charged muon or electron pairs) = 0.931 \\pm 0.026(stat.) \\pm 0.023(syst.) \\pm 0.102(lumi.) nb. Theoretical predictions, calculated at the next-to-next-to-leading order in QCD using recentmore » parton distribution functions, are in agreement with the measured cross sections. Ratios of cross sections, which incur an experimental systematic uncertainty of less than 4%, are also reported.« less

The Relationship Between Pulse Pressure, the Estimated Glomerular Filtration Rate, and Urine Microalbumin/Creatinine Ratio in Korean Adults.

PubMed

Seong, Jeong Min; Park, Chang Eun; Gi, Mi Young; Sun, Kwang Soon; Kim, Yu Jeong; Yoon, Hyun

2017-01-01

Pulse pressure (PP) is a predictor of adverse outcomes in patients on haemodialysis. Thus, the present study was conducted to assess the relationship between PP, estimated glomerular filtration rate (eGFR), and urine microalbumin/creatinine ratio (uACR) in Korean adults. Data of 9,409 adults (4,206 men and 5,203 women) aged ≥ 20 years from the Sixth Korean National Health and Nutrition Examination Survey (2013-2014) were analyzed. A multivariate analysis revealed that systolic blood pressure (SBP) (β = -0.170, 95% confidence interval [CI], -0.216 to -0.159), diastolic blood pressure (DBP) (β = 0.088, 95% CI 0.108-0.200; p < 0.001), and PP (β = -0.134, 95% CI -0.215 to -0.157) were significant factors determining eGFR. In contrast, SBP (β = 0.152, 95% CI, 0.985-1.456; p < 0.001), DBP (β = -0.062, 95% CI -1.141 to -0.442; p < 0.001), and PP (β = 0.118, 95% CI 0.965-1.436; p < 0.001) were the significant factors determining uACR. The odds ratios (ORs) of a high PP (PP ≥ 60 mmHg) with a normal group [eGFR ≥ 60 ml/min/1.73 m2 and uACR < 30 mg/g] as a reference were significant for decreased eGFR [eGFR < 60 ml/min/1.73 m2, 1.484 (95% CI, 1.003-2.196)], elevated uACR [uACR ≥ 30 mg/g, 2.592 (95% CI, 2.085-3.223)], and decreased eGFR plus elevated uACR [eGFR < 60 ml/min/1.73 m2 and uACR ≥ 30 mg/g, 3.889 (95% CI, 2.519-6.004)]. Enhanced PP was associated with a decreased eGFR and an increase in uACR in Korean adults. In addition, the PP increased greatly when a decrease in eGFR and an increase in uACR appeared simultaneously. © 2017 The Author(s). Published by S. Karger AG, Basel.

Peripheral administration of antisense oligonucleotides targeting the amyloid-β protein precursor reverses AβPP and LRP-1 overexpression in the aged SAMP8 mouse brain.

PubMed

Erickson, Michelle A; Niehoff, Michael L; Farr, Susan A; Morley, John E; Dillman, Lucy A; Lynch, Kristin M; Banks, William A

2012-01-01

The senescence accelerated mouse-prone 8 (SAMP8) mouse model of Alzheimer's disease has a natural mutation leading to age-related increases in the amyloid-β protein precursor (AβPP) and amyloid-β (Aβ) in the brain, memory impairment, and deficits in Aβ removal from the brain. Previous studies show that centrally administered antisense oligonucleotide directed against AβPP can decrease AβPP expression and Aβ production in the brains of aged SAMP8 mice, and improve memory. The same antisense crosses the blood-brain barrier and reverses memory deficits when injected intravenously. Here, we give 6 μg of AβPP or control antisense 3 times over 2 week intervals to 12 month old SAMP8 mice. Object recognition test was done 48 hours later, followed by removal of whole brains for immunoblot analysis of AβPP, low-density lipoprotein-related protein-1 (LRP-1), p-glycoprotein (Pgp), receptor for advanced glycation endproducts (RAGE), or ELISA of soluble Aβ(40). Our results show that AβPP antisense completely reverses a 30% age-associated increase in AβPP signal (p < 0.05 versus untreated 4 month old SAMP8). Soluble Aβ(40) increased with age, but was not reversed by antisense. LRP-1 large and small subunits increased significantly with age (147.7%, p < 0.01 and 123.7%, p < 0.05 respectively), and AβPP antisense completely reversed these increases (p < 0.05). Pgp and RAGE were not significantly altered with age or antisense. Antisense also caused improvements in memory (p < 0.001). Together, these data support the therapeutic potential of AβPP antisense and show a unique association between AβPP and LRP-1 expression in the SAMP8 mouse.

Immunogenicity, reactogenicity, and safety of a P1.7b,4 strain-specific serogroup B meningococcal vaccine given to preteens.

PubMed

Hosking, Jamie; Rasanathan, Kumanan; Mow, Florina Chan; Jackson, Catherine; Martin, Diana; O'Hallahan, Jane; Oster, Philipp; Ypma, Ellen; Reid, Stewart; Aaberge, Ingeborg; Crengle, Sue; Stewart, Joanna; Lennon, Diana

2007-11-01

New Zealand (NZ) has experienced a Neisseria meningitidis serogroup B epidemic since 1991. MeNZB, a strain-specific outer membrane vesicle vaccine made using an NZ epidemic strain isolate, NZ98/254 (B:4:P1.7b,4), from two manufacturing sites, the Norwegian Institute of Public Health (NIPH) and Chiron Vaccines (CV; now Novartis), was evaluated for safety, immunogenicity, and reactogenicity in this observer-blind trial with 8- to 12-year-old children. In year 1, cohort A (n = 302) was randomized 4:1 for receipt of NIPH-MeNZB or MenBvac (Norwegian parent vaccine strain 44/76; B:15:P1.7,16). In year 2, cohort B (n = 313) was randomized 4:1 for receipt of CV-MeNZB or NIPH-MeNZB. Participants all received three vaccinations 6 weeks apart. Local and systemic reactions were monitored for 7 days. Seroresponse was defined as a fourfold or greater rise in the serum bactericidal antibody titer from the baseline titer as measured by a serum bactericidal assay. Those with baseline titers of <1:4 required titers of >/=1:8 to serorespond. Intention-to-treat (ITT) and per protocol (PP) analyses are presented. In cohort A, 74% (ITT) and 73% (PP) of NIPH-MeNZB recipients demonstrated seroresponses against NZ98/254 after three doses, versus 32% (ITT and PP) of MenBvac recipients. In cohort B, seroresponses against NZ98/254 after three doses occurred in 79% (ITT and PP) of CV-MeNZB versus 75% (ITT) and 76% (PP) of NIPH-MeNZB recipients. Vaccines were tolerable, with no vaccine-related serious adverse events. In conclusion, the NZ strain meningococcal B vaccine (MeNZB) from either manufacturing site was immunogenic against New Zealand epidemic vaccine strain meningococci with no safety concerns when given in three doses to these 8- to 12-year-old children.

Immunogenicity, Reactogenicity, and Safety of a P1.7b,4 Strain-Specific Serogroup B Meningococcal Vaccine Given to Preteens▿

PubMed Central

Hosking, Jamie; Rasanathan, Kumanan; Mow, Florina Chan; Jackson, Catherine; Martin, Diana; O'Hallahan, Jane; Oster, Philipp; Ypma, Ellen; Reid, Stewart; Aaberge, Ingeborg; Crengle, Sue; Stewart, Joanna; Lennon, Diana

2007-01-01

New Zealand (NZ) has experienced a Neisseria meningitidis serogroup B epidemic since 1991. MeNZB, a strain-specific outer membrane vesicle vaccine made using an NZ epidemic strain isolate, NZ98/254 (B:4:P1.7b,4), from two manufacturing sites, the Norwegian Institute of Public Health (NIPH) and Chiron Vaccines (CV; now Novartis), was evaluated for safety, immunogenicity, and reactogenicity in this observer-blind trial with 8- to 12-year-old children. In year 1, cohort A (n = 302) was randomized 4:1 for receipt of NIPH-MeNZB or MenBvac (Norwegian parent vaccine strain 44/76; B:15:P1.7,16). In year 2, cohort B (n = 313) was randomized 4:1 for receipt of CV-MeNZB or NIPH-MeNZB. Participants all received three vaccinations 6 weeks apart. Local and systemic reactions were monitored for 7 days. Seroresponse was defined as a fourfold or greater rise in the serum bactericidal antibody titer from the baseline titer as measured by a serum bactericidal assay. Those with baseline titers of <1:4 required titers of ≥1:8 to serorespond. Intention-to-treat (ITT) and per protocol (PP) analyses are presented. In cohort A, 74% (ITT) and 73% (PP) of NIPH-MeNZB recipients demonstrated seroresponses against NZ98/254 after three doses, versus 32% (ITT and PP) of MenBvac recipients. In cohort B, seroresponses against NZ98/254 after three doses occurred in 79% (ITT and PP) of CV-MeNZB versus 75% (ITT) and 76% (PP) of NIPH-MeNZB recipients. Vaccines were tolerable, with no vaccine-related serious adverse events. In conclusion, the NZ strain meningococcal B vaccine (MeNZB) from either manufacturing site was immunogenic against New Zealand epidemic vaccine strain meningococci with no safety concerns when given in three doses to these 8- to 12-year-old children. PMID:17898183

Magnetic Induction Machines Integrated into Bulk-Micromachined Silicon

DTIC Science & Technology

2006-04-01

Actuator Workshop (Hilton Head 2000), pp. 43–7, Jun. 2000. [5] H. Guckel et al., “A first functional current excited planar rotational magnetic micromotor ...in Proc. IEEE Micro Electro Mechanical Sys- tems (MEMS’93), Feb. 1993, pp. 7–11. [6] , “Planar rotational magnetic micromotors ,” Int. J. Appl... micromotor with fully integrated stator and coils,” J. Micro- electromech. Syst., vol. 2, no. 4, pp. 165–73, Dec. 1993. [8] B. Wagner, M. Kreutzer, and W

Increased levels of IAA are required for system 2 ethylene synthesis causing fruit softening in peach (Prunus persica L. Batsch)

PubMed Central

Tatsuki, Miho

2013-01-01

The fruit of melting-flesh peach (Prunus persica L. Batsch) cultivars produce high levels of ethylene caused by high expression of PpACS1 (an isogene of 1-aminocyclopropane-1-carboxylic acid synthase), resulting in rapid fruit softening at the late-ripening stage. In contrast, the fruit of stony hard peach cultivars do not soften and produce little ethylene due to low expression of PpACS1. To elucidate the mechanism for suppressing PpACS1 expression in stony hard peaches, a microarray analysis was performed. Several genes that displayed similar expression patterns as PpACS1 were identified and shown to be indole-3-acetic acid (IAA)-inducible genes (Aux/IAA, SAUR). That is, expression of IAA-inducible genes increased at the late-ripening stage in melting flesh peaches; however, these transcripts were low in mature fruit of stony hard peaches. The IAA concentration increased suddenly just before harvest time in melting flesh peaches exactly coinciding with system 2 ethylene production. In contrast, the IAA concentration did not increase in stony hard peaches. Application of 1-naphthalene acetic acid, a synthetic auxin, to stony hard peaches induced a high level of PpACS1 expression, a large amount of ethylene production and softening. Application of an anti-auxin, α-(phenylethyl-2-one)-IAA, to melting flesh peaches reduced levels of PpACS1 expression and ethylene production. These observations indicate that suppression of PpACS1 expression at the late-ripening stage of stony hard peach may result from a low level of IAA and that a high concentration of IAA is required to generate a large amount of system 2 ethylene in peaches. PMID:23364941

Role of Scd5, a protein phosphatase-1 targeting protein, in phosphoregulation of Sla1 during endocytosis

PubMed Central

Chi, Richard J.; Torres, Onaidy T.; Segarra, Verónica A.; Lansley, Tanya; Chang, Ji Suk; Newpher, Thomas M.; Lemmon, Sandra K.

2012-01-01

Summary Phosphorylation regulates assembly and disassembly of proteins during endocytosis. In yeast, Prk1 and Ark1 phosphorylate factors after vesicle internalization leading to coat disassembly. Scd5, a protein phosphatase-1 (PP1)-targeting subunit, is proposed to regulate dephosphorylation of Prk1/Ark1 substrates to promote new rounds of endocytosis. In this study we analyzed scd5-PP1Δ2, a mutation causing impaired PP1 binding. scd5-PP1Δ2 caused hyperphosphorylation of several Prk1 endocytic targets. Live-cell imaging of 15 endocytic components in scd5-PP1Δ2 revealed that most factors arriving before the invagination/actin phase of endocytosis had delayed lifetimes. Severely affected were early factors and Sla2 (Hip1R homolog), whose lifetime was extended nearly fourfold. In contrast, the lifetime of Sla1, a Prk1 target, was extended less than twofold, but its cortical recruitment was significantly reduced. Delayed Sla2 dynamics caused by scd5-PP1Δ2 were suppressed by SLA1 overexpression. This was dependent on the LxxQxTG repeats (SR) of Sla1, which are phosphorylated by Prk1 and bind Pan1, another Prk1 target, in the dephosphorylated state. Without the SR, Sla1ΔSR was still recruited to the cell surface, but was less concentrated in cortical patches than Pan1. sla1ΔSR severely impaired endocytic progression, but this was partially suppressed by overexpression of LAS17, suggesting that without the SR region the SH3 region of Sla1 causes constitutive negative regulation of Las17 (WASp). These results demonstrate that Scd5/PP1 is important for recycling Prk1 targets to initiate new rounds of endocytosis and provide new mechanistic information on the role of the Sla1 SR domain in regulating progression to the invagination/actin phase of endocytosis. PMID:22825870

The neural correlates of biomechanical constraints in hand laterality judgment task performed from other person's perspective: A near-infrared spectroscopy study.

PubMed

Meng, Shuang; Oi, Misato; Saito, Godai; Saito, Hirofumi

2017-01-01

Previous studies, mainly using a first-person perspective (1PP), have shown that the judgments of the hand laterality judgment (HLJ) task are dependent on biomechanical constraints (BC). Specifically, differing reaction times (RT) for hand pictures rotated medially or laterally around the mid sagittal plane are attributed to the BC effect on motor imagery. In contrast, we investigated whether the HLJ task is also subject to BC when performed from a third-person perspective (3PP) as well as 1PP using near-infrared spectroscopy (NIRS) to measure the brain activity of prefrontal cortex (PFC) in right-handed participants assigned to 1PP or 3PP groups. The 1PP group judged whether a presented hand was their own left or right hand, and the 3PP group whether it was the other's left or right hand. Using their HLJ task error rates, the 1PP and 3PP groups were subdivided into an Error Group (EG) and No Error Group (NEG). For the 1PP group, both EG and NEG showed a significant Hand Laterality × Orientation interaction for RT, indicating the BC effect on motor imagery. For the 3PP group, however, neither EG nor NEG showed the interaction, even though EG showed a significantly longer RT than NEG. These results suggest that the 3PP EG appropriately followed the 3PP task instruction, while the NEG might have taken 1PP. However, the 3PP EG NIRS profile of left PFC showed a significant Hand Laterality × Orientation interaction, while the 1PP EG did not. More noteworthy is that the left PFC activation of EG showed an interaction between the 1PP and 3PP groups when the left hand was presented. Furthermore, in the NEG, the PFC activation was not influenced by the BC in either the 1PP or 3PP condition. These results indicate that BC interferes with the HLJ task performed from the 1PP and 3PP.

Effect of simulated pulpal pressure on all-in-one adhesive bond strengths to dentine.

PubMed

Hosaka, Keiichi; Nakajima, Masatoshi; Yamauti, Monica; Aksornmuang, Juthatip; Ikeda, Masaomi; Foxton, Richard M; Pashley, David H; Tagami, Junji

2007-03-01

To evaluate the durability of all-in-one adhesive systems bonded to dentine with and without simulated hydrostatic pulpal pressure (PP). Flat dentine surfaces of extracted human molars were prepared. Two all-in-one adhesive systems, One-Up Bond F (OBF) (Tokuyama Corp., Tokyo, Japan), and Fluoro Bond Shake One (FBS) (Shofu Co., Kyoto, Japan) were applied to the dentine surfaces under either a PP of 0 or 15cm H(2)O. Then, resin composite build-ups were made. The specimens bonded under pressure were stored in 37 degrees C water for 24h, 1 and 3 months under 15cm H(2)O PP. Specimens not bonded under pressure were stored under zero PP. After storage, the specimens were sectioned into slabs that were trimmed to hourglass shapes and subjected to micro-tensile bond testing (muTBS). The data were analysed using two-way ANOVA and Holm-Sidak HSD multiple comparison tests (alpha=0.05). The muTBS of OBF fell significantly (p<0.05) when PP was applied during bonding and storage, regardless of storage time. In contrast, although the muTBS of OBF specimens bonded and stored without hydrostatic pressure storage fell significantly over the 3 months period, the decrease was less than half as much as specimens stored under PP. In FBS bonded specimens, although there was no significant difference between the muTBS with and without hydrostatic pulpal pressure at 24h, by 1 and 3 months of storage under PP, significant reductions were seen compared with the control group without PP. The muTBS of OBF bonded specimens was lowered more by simulated PP than by storage time; specimens bonded with FBS were not sensitive to storage time in the absence of PP, but showed lower bond strengths at 1 and 3 months in the presence of PP.

Characterization of 9H-(1,3-dichlor-9, 9-dimethylacridin-2-ona-7-yl)-phosphate (DDAO) as substrate of PP-2A in a fluorimetric microplate assay for diarrhetic shellfish toxins (DSP).

PubMed

Leira, F; Vieites, J M; Vieytes, M R; Botana, L M

2000-12-01

Specific inhibition of protein-phosphatases by diarrhetic shellfish toxins (DSP) of the okadaic acid group, has led to the development of a fluorescent enzyme inhibition assay for these toxins using protein-phosphatase 2A (PP-2A) and fluorogenic substrates of the enzyme. Two different substrates of PP-2A have been previously used in this microplate assay: 4-methylumbelliferyl phosphate and fluorescein diphosphate (FDP). In this report, we present the results obtained using a new fluorogenic substrate of PP-2A, the compound dimethylacridinone phosphate (DDAO). A linear relationship between PP-2A concentration and DDAO-induced fluorescence was observed. Okadaic acid (0.0157-9.43 nM)-dependent inhibition of phosphatase activity showed similar results using FDP and DDAO. Recovery percentages obtained with FDP and DDAO in spiked mussel samples (both raw and canned) were very similar and reproducible. Comparative analysis of DSP-contaminated mussel samples by HPLC and FDP/DDAO-PP-2A showed a good correlation among all methods, thus demonstrating that DDAO can be used as a fluorogenic substrate to quantify okadaic acid and related toxins in bivalve molluscs with optimum reliability.

A protein phosphatase feedback mechanism regulates the basal phosphorylation of Chk2 kinase in the absence of DNA damage.

PubMed

Carlessi, Luigi; Buscemi, Giacomo; Fontanella, Enrico; Delia, Domenico

2010-10-01

The checkpoint kinase Chk2 is an effector component of the ATM-dependent DNA damage response (DDR) pathway. The activation of Chk2 by genotoxic stress involves its phosphorylation on T68 by ATM and additional auto/transphosphorylations. Here we demonstrate that in unperturbed cells, chemical inhibition of Chk2 by VRX0466617 (VRX) enhances the phosphorylation of Chk2-T68 throughout the cell cycle phases. This event, dependent on the presence of ATM and catalytically functional Chk2, is not consequential to DNA damage, as neither gamma-H2AX nuclear foci nor increased ATM activation is detected in VRX-treated cells, suggesting the involvement of other regulatory proteins. As serine/threonine protein phosphatases (PPs) regulate the phosphorylation and deactivation of proteins of the DDR pathway, we analyzed their role in phospho-T68-Chk2 regulation. We found that intracellular inhibition of PP1 and PP2A-like activities by okadaic acid markedly raised the accumulation of Chk2-pT68 without DNA damage induction, and this phenomenon was also seen when PP1-C, PP2A-C, and Wip1/PPM1D were simultaneously knockdown by siRNA. Altogether, these data indicate a novel mechanism in undamaged cells where PPs function to maintain the balance between ATM and its direct substrate Chk2 through a regulatory circuit. Copyright © 2010 Elsevier B.V. All rights reserved.

JPRS Report, Science & Technology China

DTIC Science & Technology

1989-02-02

40091007b Beijing WEISHENGWU XUEBAO [ACTA MICROBIOLOGICA SINICA] in Chinese Vol 28 No 3, Sep 88 pp 257- 264 [English abstract of article by Gong Jianhua...G.H., KAPL-M-SMS-31, 1956, pp 4-6. 4. Caldwell, C.S., WAPD -CP-1030, 1956, pp 1-5. 5. Himmelblau, D.M., et al., J. CHEM. ENG. DATA, Vol 5 No 1, 1

Measurement of the B ± Meson Nuclear Modification Factor in Pb-Pb Collisions at s N N = 5.02 TeV

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sirunyan, A. M.; Tumasyan, A.; Adam, W.

The differential production cross sections of B± mesons are measured via the exclusive decay channels B ± → J/ψK ± → μ +μ -K ± as a function of transverse momentum in pp and Pb-Pb collisions at a center-of-mass energy √ sNN = 5.02 TeV per nucleon pair with the CMS detector at the LHC. The pp(Pb-Pb) data set used for this analysis corresponds to an integrated luminosity of 28.0 pb -1 (351 μb -1). The measurement is performed in the B ± meson transverse momentum range of 7 to 50 GeV/c, in the rapidity interval |y|<2.4. In this kinematicmore » range, a strong suppression of the production cross section by about a factor of 2 is observed in the Pb-Pb system in comparison to the expectation from pp reference data. Finally, these results are found to be roughly compatible with theoretical calculations incorporating beauty quark diffusion and energy loss in a quark-gluon plasma.« less

Measurement of the B ± Meson Nuclear Modification Factor in Pb-Pb Collisions at s N N = 5.02 TeV

DOE PAGES

Sirunyan, A. M.; Tumasyan, A.; Adam, W.; ...

2017-10-13

The differential production cross sections of B± mesons are measured via the exclusive decay channels B ± → J/ψK ± → μ +μ -K ± as a function of transverse momentum in pp and Pb-Pb collisions at a center-of-mass energy √ sNN = 5.02 TeV per nucleon pair with the CMS detector at the LHC. The pp(Pb-Pb) data set used for this analysis corresponds to an integrated luminosity of 28.0 pb -1 (351 μb -1). The measurement is performed in the B ± meson transverse momentum range of 7 to 50 GeV/c, in the rapidity interval |y|<2.4. In this kinematicmore » range, a strong suppression of the production cross section by about a factor of 2 is observed in the Pb-Pb system in comparison to the expectation from pp reference data. Finally, these results are found to be roughly compatible with theoretical calculations incorporating beauty quark diffusion and energy loss in a quark-gluon plasma.« less

Time trends in utilization of G-CSF prophylaxis and risk of febrile neutropenia in a Medicare population receiving adjuvant chemotherapy for early-stage breast cancer.

PubMed

Goyal, Ravi K; Tzivelekis, Spiros; Rothman, Kenneth J; Candrilli, Sean D; Kaye, James A

2018-02-01

The purpose of this study is to assess temporal trends in the use of granulocyte colony-stimulating factor (G-CSF) prophylaxis and risk of febrile neutropenia (FN) among older women receiving adjuvant chemotherapy for early-stage breast cancer. Women aged ≥ 66 years with diagnosis of early-stage breast cancer who initiated selected adjuvant chemotherapy regimens were identified using the SEER-Medicare data from 2002 to 2012. Adjusted, calendar-year-specific proportions were estimated for use of G-CSF primary prophylaxis (PP) and secondary prophylaxis and FN risk in the first and the second/subsequent cycles during the first course of chemotherapy, using logistic regression models. calendar-year-specific mean probabilities were estimated with covariates set to modal values. Among 11,107 eligible patients (mean age 71.7 years), 74% received G-CSF in the first course of chemotherapy. Of all patients, 5819 (52%) received G-CSF PP, and among those not receiving G-CSF PP, only 5% received G-CSF secondary prophylaxis. The adjusted proportion using G-CSF PP increased from 6% in 2002 to 71% in 2012. During the same period, the adjusted risk of FN in the first cycle increased from 2% to 3%; the adjusted risk increased from 1.5% to 2.9% among those receiving G-CSF PP and from 2.3% to 3.5% among those not receiving G-CSF PP. The use of G-CSF PP increased substantially during the study period. Although channeling of higher-risk patients to treatment with G-CSF PP is expected, the adjusted risk of FN among patients treated with G-CSF PP tended to be lower than among those not receiving G-CSF PP.

24-h pulse pressure cutoff point definition by office pulse pressure in a population of Spanish older hypertensive patients.

PubMed

Vinyoles, Ernest; de la Sierra, Alejandro; Roso-Llorach, Albert; Banegas, José R; de la Cruz, Juan José; Gorostidi, Manuel; Segura, Julián; Divisón, Juan Antonio; Ruíz-Hurtado, Gema; Ruilope, Luis Miguel

2017-05-01

The European Guidelines on Hypertension define an office pulse pressure (PP) at least 60 mmHg in the elderly patient as asymptomatic organ damage. Our objective was to estimate the cutoff point of 24-h PP that best predicts office PP associated with higher cardiovascular risk (≥60 mmHg) in hypertensive older patients. We studied all hypertensive patients at least 60 years with a first valid ambulatory blood pressure monitoring drawn from the Spanish ambulatory blood pressure monitoring registry. Receiver operating characteristic curves were used to estimate the best 24-h PP cutoff predictor of office PP at least 60 mmHg that maximized the sum of sensitivity and specificity. We included 52 246 hypertensive patients [52.4%, female; mean age (SD) 69.0 (7.0) years]. From these, 34 530 (66.1%) patients had an office PP at least 60 mmHg. The value of 24-h PP that best predicts higher risk clinic PP is 54.9 mmHg [sensitivity: 69.2%; specificity: 70.3%; area under the receiver operating characteristic curve of 0.761 (95% confidence interval 0.756-0.765)]. Mean clinic and 24-h PPs were progressively higher as the study participants were classified at higher cardiovascular risk group. Some 20.5% of patients presented isolated office high PP and 10% a masked high 24-h PP. In a large clinical sample of older hypertensive patients, the cutoff point of 24-h PP that best predicts office PP at least 60 mmHg is 55 mmHg. In 30.5% of cases, there is a discrepancy between office PP and ambulatory 24-h PP.

Analysis of Vernier Scans during the PP2PP run in 2009 (pp at 100 GeV/beam)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Drees, A.

2011-12-13

At the end of RHIC's 2009 operation a dedicated run for the PP2PP experiment (part of the STAR experiment) took place from Jun 29 to Jul 06 2009. Polarized protons were accelerated to 100 GeV using ramp-file pp100-90pp2pp with a {beta}* = 22 m in IR6. Since only transverse polarization was required no rotator ramp was in use. The PP2PP experiment consists mainly of two Roman Pot detectors (one horizontal and one vertical) on either side of IR6 in the outgoing-beam arms between the Q3 and Q4 magnets. The yellow pots are in sector 5, the blue ones in sectormore » 6. Roman Pot type detectors are installed inside the beampipe causing an accelerator safety concern. To address this concern there is a limit to the allowable total beam current in the machine while Roman Pots are enabled to move closer to the beam. This limit was set to a motion limit of 5 mm from the center of the beampipe and 50 {center_dot} 10{sup 11} beam current per ring. In order to reduce the background in the detectors, beams were scraped using the RHIC collimator system prior to moving the pots closer. This was typically repeated several times throughout a store since beam halo reforms over the course of hours.« less

Oxidative impairment of hippocampal long-term potentiation involves activation of protein phosphatase 2A and is prevented by ketone bodies.

PubMed

Maalouf, Marwan; Rho, Jong M

2008-11-15

Previous studies have shown that ketone bodies (KB) exert antioxidant effects in experimental models of neurological disease. In the present study, we explored the effects of the KB acetoacetate (ACA) and beta-hydroxybutyrate (BHB) on impairment of hippocampal long-term potentiation (LTP) in rats by hydrogen peroxide (H(2)O(2)) using electrophysiological, fluorescence imaging, and enzyme assay techniques. We found that: 1) a combination of ACA and BHB (1 mM each) prevented impairment of LTP by H(2)O(2) (200 microM); 2) KB significantly lowered intracellular levels of reactive oxygen species (ROS)--measured with the fluorescent indicator carboxy-H(2)DCFDA (carboxy-2',7'-dichlorodihydrofluorescein diacetate)--in CA1 pyramidal neurons exposed to H(2)O(2); 3) the effect of KB on LTP was replicated by the protein phosphatase 2A (PP2A) inhibitor fostriecin; 4) KB prevented impairment of LTP by the PP2A activator C(6) ceramide; 5) fostriecin did not prevent the increase in ROS levels in CA1 pyramidal neurons exposed to H(2)O(2), and C(6) ceramide did not increase ROS levels; 6) PP2A activity was enhanced by both H(2)O(2) and rotenone (a mitochondrial complex I inhibitor that increases endogenous superoxide production); and 7) KB inhibited PP2A activity in protein extracts from brain tissue treated with either H(2)O(2) or ceramide. We propose that oxidative impairment of hippocampal LTP is associated with PP2A activation, and that KB prevent this impairment in part by inducing PP2A inhibition through an antioxidant mechanism.

Standardised extract of Bacopa monniera (CDRI-08) improves contextual fear memory by differentially regulating the activity of histone acetylation and protein phosphatases (PP1α, PP2A) in hippocampus.

PubMed

Preethi, Jayakumar; Singh, Hemant K; Venkataraman, Jois Shreyas; Rajan, Koilmani Emmanuvel

2014-05-01

Contextual fear conditioning is a paradigm for investigating cellular mechanisms involved in hippocampus-dependent memory. Earlier, we showed that standardised extract of Bacopa monniera (CDRI-08) improves hippocampus-dependent learning in postnatal rats by elevating the level of serotonin (5-hydroxytryptamine, 5-HT), activate 5-HT3A receptors, and cyclic adenosine monophosphate (cAMP) response element binding (CREB) protein. In this study, we have further examined the molecular mechanism of CDRI-08 in hippocampus-dependent memory and compared to the histone deacetylase (HDACs) inhibitor sodium butyrate (NaB). To assess the hippocampus-dependent memory, wistar rat pups were subjected to contextual fear conditioning (CFC) following daily (postnatal days 15-29) administration of vehicle solution (0.5 % gum acacia + 0.9 % saline)/CDRI-08 (80 mg/kg, p.o.)/NaB (1.2 g/kg in PBS, i.p.). CDRI-08/NaB treated group showed enhanced freezing behavior compared to control group when re-exposed to the same context. Administration of CDRI-08/NaB resulted in activation of extracellular signal-regulated kinase ERK/CREB signaling cascade and up-regulation of p300, Ac-H3 and Ac-H4 levels, and down-regulation of HDACs (1, 2) and protein phosphatases (PP1α, PP2A) in hippocampus following CFC. This would subsequently result in an increased brain-derived neurotrophic factor (Bdnf) (exon IV) mRNA in hippocampus. Altogether, our results indicate that CDRI-08 enhances hippocampus-dependent contextual memory by differentially regulating histone acetylation and protein phosphatases in hippocampus.

Theoretical research into anticancer activity of diterpenes isolated from the paraiban flora.

PubMed

Ishiki, Hamilton; Junior, Francisco J B Mendonça; Santos, Paula F; Tavares, Josean F; Tavares, Josean F; Silva, Marcelo S; Scotti, Marcus T

2014-07-01

Many studies of the scientific literature discuss the anticancer activity of diterpenes inhibiting the Akt/IKK/NF-kappaB pro-survival signaling cascade, mainly by the activation of serine/threonine phosphatase PP2A. The aim of this work was to evaluate and compare the anticancer potential of three atisane, three kaurane and three trachylobane diterpenes extracted from the roots of Xylopia langsdorffiana. Thus, we investigated the reactivity (H-L(GAP) parameter), HOMO atmosphere favorable to neutralize the radical reactivity, and the docking of compounds with PP2A. With all approaches, this theoretical study showed that atisane diterpenes have favorable characteristics for antitumor activity, like electron donating ability and greater hydrophilic interactions with the enzyme, by inhibition of Akt/IKK/NF-kappaB, and activation of PP2A.

Structural basis and functions of abscisic acid receptors PYLs

PubMed Central

Zhang, Xing L.; Jiang, Lun; Xin, Qi; Liu, Yang; Tan, Jian X.; Chen, Zhong Z.

2015-01-01

Abscisic acid (ABA) plays a key role in many developmental processes and responses to adaptive stresses in plants. Recently, a new family of nucleocytoplasmic PYR/PYL/RCAR (PYLs) has been identified as bona fide ABA receptors. PYLs together with protein phosphatases type-2C (PP2Cs), Snf1 (Sucrose-non-fermentation 1)-related kinases subfamily 2 (SnRK2s) and downstream substrates constitute the core ABA signaling network. Generally, PP2Cs inactivate SnRK2s kinases by physical interaction and direct dephosphorylation. Upon ABA binding, PYLs change their conformations and then contact and inhibit PP2Cs, thus activating SnRK2s. Here, we reviewed the recent progress in research regarding the structures of the core signaling pathways of ABA, including the (+)-ABA, (−)-ABA and ABA analogs pyrabactin as well as 6AS perception by PYLs, SnRK2s mimicking PYLs in binding PP2Cs. PYLs inhibited PP2Cs in both the presence and absence of ABA and activated SnRK2s. The present review elucidates multiple ABA signal perception and transduction by PYLs, which might shed light on how to design small chemical compounds for improving plant performance in the future. PMID:25745428

ABI1 and PP2CA Phosphatases Are Negative Regulators of Snf1-Related Protein Kinase1 Signaling in Arabidopsis[C][W

PubMed Central

Rodrigues, Américo; Adamo, Mattia; Crozet, Pierre; Margalha, Leonor; Confraria, Ana; Martinho, Cláudia; Elias, Alexandre; Rabissi, Agnese; Lumbreras, Victoria; González-Guzmán, Miguel; Antoni, Regina; Rodriguez, Pedro L.; Baena-González, Elena

2013-01-01

Plant survival under environmental stress requires the integration of multiple signaling pathways into a coordinated response, but the molecular mechanisms underlying this integration are poorly understood. Stress-derived energy deprivation activates the Snf1-related protein kinases1 (SnRK1s), triggering a vast transcriptional and metabolic reprogramming that restores homeostasis and promotes tolerance to adverse conditions. Here, we show that two clade A type 2C protein phosphatases (PP2Cs), established repressors of the abscisic acid (ABA) hormonal pathway, interact with the SnRK1 catalytic subunit causing its dephosphorylation and inactivation. Accordingly, SnRK1 repression is abrogated in double and quadruple pp2c knockout mutants, provoking, similarly to SnRK1 overexpression, sugar hypersensitivity during early seedling development. Reporter gene assays and SnRK1 target gene expression analyses further demonstrate that PP2C inhibition by ABA results in SnRK1 activation, promoting SnRK1 signaling during stress and once the energy deficit subsides. Consistent with this, SnRK1 and ABA induce largely overlapping transcriptional responses. Hence, the PP2C hub allows the coordinated activation of ABA and energy signaling, strengthening the stress response through the cooperation of two key and complementary pathways. PMID:24179127

Activation of tumor suppressor protein PP2A inhibits KRAS-driven tumor growth

PubMed Central

Sangodkar, Jaya; Perl, Abbey; Tohme, Rita; Kiselar, Janna; Kastrinsky, David B.; Izadmehr, Sudeh; Mazhar, Sahar; Wiredja, Danica D.; O’Connor, Caitlin M.; Hoon, Divya; Dhawan, Neil S.; Schlatzer, Daniela; Yao, Shen; Leonard, Daniel; Borczuk, Alain C.; Gokulrangan, Giridharan; Wang, Lifu; Svenson, Elena; Farrington, Caroline C.; Yuan, Eric; Avelar, Rita A.; Stachnik, Agnes; Smith, Blake; Gidwani, Vickram; Giannini, Heather M.; McQuaid, Daniel; McClinch, Kimberly; Wang, Zhizhi; Levine, Alice C.; Sears, Rosalie C.; Chen, Edward Y.; Duan, Qiaonan; Datt, Manish; Ma’ayan, Avi; DiFeo, Analisa; Sharma, Neelesh; Galsky, Matthew D.; Brautigan, David L.; Ioannou, Yiannis A.; Xu, Wenqing; Chance, Mark R.; Ohlmeyer, Michael

2017-01-01

Targeted cancer therapies, which act on specific cancer-associated molecular targets, are predominantly inhibitors of oncogenic kinases. While these drugs have achieved some clinical success, the inactivation of kinase signaling via stimulation of endogenous phosphatases has received minimal attention as an alternative targeted approach. Here, we have demonstrated that activation of the tumor suppressor protein phosphatase 2A (PP2A), a negative regulator of multiple oncogenic signaling proteins, is a promising therapeutic approach for the treatment of cancers. Our group previously developed a series of orally bioavailable small molecule activators of PP2A, termed SMAPs. We now report that SMAP treatment inhibited the growth of KRAS-mutant lung cancers in mouse xenografts and transgenic models. Mechanistically, we found that SMAPs act by binding to the PP2A Aα scaffold subunit to drive conformational changes in PP2A. These results show that PP2A can be activated in cancer cells to inhibit proliferation. Our strategy of reactivating endogenous PP2A may be applicable to the treatment of other diseases and represents an advancement toward the development of small molecule activators of tumor suppressor proteins. PMID:28504649

Nitrogen metabolism of two contrasting poplar species during acclimation to limiting nitrogen availability

PubMed Central

Luo, Zhi-Bin

2013-01-01

To investigate N metabolism of two contrasting Populus species in acclimation to low N availability, saplings of slow-growing species (Populus popularis, Pp) and a fast-growing species (Populus alba × Populus glandulosa, Pg) were exposed to 10, 100, or 1000 μM NH4NO3. Despite greater root biomass and fine root surface area in Pp, lower net influxes of NH4 + and NO3 – at the root surface were detected in Pp compared to those in Pg, corresponding well to lower NH4 + and NO3 – content and total N concentration in Pp roots. Meanwhile, higher stable N isotope composition (δ15N) in roots and stronger responsiveness of transcriptional regulation of 18 genes involved in N metabolism were found in roots and leaves of Pp compared to those of Pg. These results indicate that the N metabolism of Pp is more sensitive to decreasing N availability than that of Pg. In both species, low N treatments decreased net influxes of NH4 + and NO3 –, root NH4 + and foliar NO3 – content, root NR activities, total N concentration in roots and leaves, and transcript levels of most ammonium (AMTs) and nitrate (NRTs) transporter genes in leaves and genes involved in N assimilation in roots and leaves. Low N availability increased fine root surface area, foliar starch concentration, δ15N in roots and leaves, and transcript abundance of several AMTs (e.g. AMT1;2) and NRTs (e.g. NRT1;2 and NRT2;4B) in roots of both species. These data indicate that poplar species slow down processes of N acquisition and assimilation in acclimation to limiting N supply. PMID:23963674

German Special Operations in the 1944 Ardennes Offensive

DTIC Science & Technology

1994-06-03

Britain Prints Int. Ltd., 1984), pp. 67-68. 31 1SGerald Astor , A Blood-Dimmed Tide (USA: Donald L Fine, Inc., 1992), pp.70-71. 191bd., p. 70. 20%d., p...pp. 78-80. 3 1 Skom=ny, pp.158-159. 3 2Ibid., p.159. 331bid.. 3 4 Gerald Astor , A Blood Dimmed Tide (USA: Donald L Fine Inc., 1992), p. 66. 55...special operations did have some favorable impact on the campaign, they were unable to assist the conventional forces in rei *g any of the key campaign

Measurement of sigma Lambda b0/sigma B0 x B(Lambda b0-->Lambda c+pi-)/B(B0-->D+pi-) in pp collisions at square root s=1.96 TeV.

PubMed

Abulencia, A; Adelman, J; Affolder, T; Akimoto, T; Albrow, M G; Ambrose, D; Amerio, S; Amidei, D; Anastassov, A; Anikeev, K; Annovi, A; Antos, J; Aoki, M; Apollinari, G; Arguin, J-F; Arisawa, T; Artikov, A; Ashmanskas, W; Attal, A; Azfar, F; Azzi-Bacchetta, P; Azzurri, P; Bacchetta, N; Badgett, W; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Baroiant, S; Bartsch, V; Bauer, G; Bedeschi, F; Behari, S; Belforte, S; Bellettini, G; Bellinger, J; Belloni, A; Benjamin, D; Beretvas, A; Beringer, J; Berry, T; Bhatti, A; Binkley, M; Bisello, D; Blair, R E; Blocker, C; Blumenfeld, B; Bocci, A; Bodek, A; Boisvert, V; Bolla, G; Bolshov, A; Bortoletto, D; Boudreau, J; Boveia, A; Brau, B; Brigliadori, L; Bromberg, C; Brubaker, E; Budagov, J; Budd, H S; Budd, S; Budroni, S; Burkett, K; Busetto, G; Bussey, P; Byrum, K L; Cabrera, S; Campanelli, M; Campbell, M; Canelli, F; Canepa, A; Carillo, S; Carlsmith, D; Carosi, R; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chang, S H; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, I; Cho, K; Chokheli, D; Chou, J P; Choudalakis, G; Chuang, S H; Chung, K; Chung, W H; Chung, Y S; Ciljak, M; Ciobanu, C I; Ciocci, M A; Clark, A; Clark, D; Coca, M; Compostella, G; Convery, M E; Conway, J; Cooper, B; Copic, K; Cordelli, M; Cortiana, G; Crescioli, F; Cuenca Almenar, C; Cuevas, J; Culbertson, R; Cully, J C; Cyr, D; DaRonco, S; D'Auria, S; Davies, T; D'Onofrio, M; Dagenhart, D; de Barbaro, P; De Cecco, S; Deisher, A; De Lentdecker, G; Dell'Orso, M; Delli Paoli, F; Demortier, L; Deng, J; Deninno, M; De Pedis, D; Derwent, P F; Di Giovanni, G P; Dionisi, C; Di Ruzza, B; Dittmann, J R; DiTuro, P; Dörr, C; Donati, S; Donega, M; Dong, P; Donini, J; Dorigo, T; Dube, S; Efron, J; Erbacher, R; Errede, D; Errede, S; Eusebi, R; Fang, H C; Farrington, S; Fedorko, I; Fedorko, W T; Feild, R G; Feindt, M; Fernandez, J P; Field, R; Flanagan, G; Foland, A; Forrester, S; Foster, G W; Franklin, M; Freeman, J C; Furic, I; Gallinaro, M; Galyardt, J; Garcia, J E; Garberson, F; Garfinkel, A F; Gay, C; Gerberich, H; Gerdes, D; Giagu, S; Giannetti, P; Gibson, A; Gibson, K; Gimmell, J L; Ginsburg, C; Giokaris, N; Giordani, M; Giromini, P; Giunta, M; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldschmidt, N; Goldstein, J; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gresele, A; Griffiths, M; Grinstein, S; Grosso-Pilcher, C; Group, R C; Grundler, U; Guimaraes da Costa, J; Gunay-Unalan, Z; Haber, C; Hahn, K; Hahn, S R; Halkiadakis, E; Hamilton, A; Han, B-Y; Han, J Y; Handler, R; Happacher, F; Hara, K; Hare, M; Harper, S; Harr, R F; Harris, R M; Hartz, M; Hatakeyama, K; Hauser, J; Heijboer, A; Heinemann, B; Heinrich, J; Henderson, C; Herndon, M; Heuser, J; Hidas, D; Hill, C S; Hirschbuehl, D; Hocker, A; Holloway, A; Hou, S; Houlden, M; Hsu, S-C; Huffman, B T; Hughes, R E; Husemann, U; Huston, J; Incandela, J; Introzzi, G; Iori, M; Ishizawa, Y; Ivanov, A; Iyutin, B; James, E; Jang, D; Jayatilaka, B; Jeans, D; Jensen, H; Jeon, E J; Jindariani, S; Jones, M; Joo, K K; Jun, S Y; Jung, J E; Junk, T R; Kamon, T; Karchin, P E; Kato, Y; Kemp, Y; Kephart, R; Kerzel, U; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kimura, N; Kirsch, L; Klimenko, S; Klute, M; Knuteson, B; Ko, B R; Kondo, K; Kong, D J; Konigsberg, J; Korytov, A; Kotwal, A V; Kovalev, A; Kraan, A C; Kraus, J; Kravchenko, I; Kreps, M; Kroll, J; Krumnack, N; Kruse, M; Krutelyov, V; Kubo, T; Kuhlmann, S E; Kuhr, T; Kusakabe, Y; Kwang, S; Laasanen, A T; Lai, S; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; Lazzizzera, I; Le, Y; LeCompte, T; Lee, J; Lee, J; Lee, Y J; Lee, S W; Lefèvre, R; Leonardo, N; Leone, S; Levy, S; Lewis, J D; Lin, C; Lin, C S; Lindgren, M; Lipeles, E; Lister, A; Litvintsev, D O; Liu, T; Lockyer, N S; Loginov, A; Loreti, M; Loverre, P; Lu, R-S; Lucchesi, D; Lujan, P; Lukens, P; Lungu, G; Lyons, L; Lys, J; Lysak, R; Lytken, E; Mack, P; MacQueen, D; Madrak, R; Maeshima, K; Makhoul, K; Maki, T; Maksimovic, P; Malde, S; Manca, G; Margaroli, F; Marginean, R; Marino, C; Marino, C P; Martin, A; Martin, M; Martin, V; Martínez, M; Maruyama, T; Mastrandrea, P; Masubuchi, T; Matsunaga, H; Mattson, M E; Mazini, R; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Menzemer, S; Menzione, A; Merkel, P; Mesropian, C; Messina, A; Miao, T; Miladinovic, N; Miles, J; Miller, R; Mills, C; Milnik, M; Mitra, A; Mitselmakher, G; Miyamoto, A; Moed, S; Moggi, N; Mohr, B; Moore, R; Morello, M; Movilla Fernandez, P; Mülmenstädt, J; Mukherjee, A; Muller, Th; Mumford, R; Murat, P; Nachtman, J; Nagano, A; Naganoma, J; Nakano, I; Napier, A; Necula, V; Neu, C; Neubauer, M S; Nielsen, J; Nigmanov, T; Nodulman, L; Norniella, O; Nurse, E; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Oldeman, R; Orava, R; Osterberg, K; Pagliarone, C; Palencia, E; Papadimitriou, V; Paramonov, A A; Parks, B; Pashapour, S; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Piedra, J; Pinera, L; Pitts, K; Plager, C; Pondrom, L; Portell, X; Poukhov, O; Pounder, N; Prakoshyn, F; Pronko, A; Proudfoot, J; Ptohos, F; Punzi, G; Pursley, J; Rademacker, J; Rahaman, A; Ranjan, N; Rappoccio, S; Reisert, B; Rekovic, V; Renton, P; Rescigno, M; Richter, S; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rogers, E; Rolli, S; Roser, R; Rossi, M; Rossin, R; Ruiz, A; Russ, J; Rusu, V; Saarikko, H; Sabik, S; Safonov, A; Sakumoto, W K; Salamanna, G; Saltó, O; Saltzberg, D; Sánchez, C; Santi, L; Sarkar, S; Sartori, L; Sato, K; Savard, P; Savoy-Navarro, A; Scheidle, T; Schlabach, P; Schmidt, E E; Schmidt, M P; Schmitt, M; Schwarz, T; Scodellaro, L; Scott, A L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semenov, A; Sexton-Kennedy, L; Sfyrla, A; Shapiro, M D; Shears, T; Shepard, P F; Sherman, D; Shimojima, M; Shochet, M; Shon, Y; Shreyber, I; Sidoti, A; Sinervo, P; Sisakyan, A; Sjolin, J; Slaughter, A J; Slaunwhite, J; Sliwa, K; Smith, J R; Snider, F D; Snihur, R; Soderberg, M; Soha, A; Somalwar, S; Sorin, V; Spalding, J; Spinella, F; Spreitzer, T; Squillacioti, P; Stanitzki, M; Staveris-Polykalas, A; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Stuart, D; Suh, J S; Sukhanov, A; Sun, H; Suzuki, T; Taffard, A; Takashima, R; Takeuchi, Y; Takikawa, K; Tanaka, M; Tanaka, R; Tecchio, M; Teng, P K; Terashi, K; Thom, J; Thompson, A S; Thomson, E; Tipton, P; Tiwari, V; Tkaczyk, S; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Tourneur, S; Trischuk, W; Tseng, J; Tsuchiya, R; Tsuno, S; Turini, N; Ukegawa, F; Unverhau, T; Uozumi, S; Usynin, D; Vallecorsa, S; van Remortel, N; Varganov, A; Vataga, E; Vázquez, F; Velev, G; Veramendi, G; Veszpremi, V; Vidal, R; Vila, I; Vilar, R; Vine, T; Vollrath, I; Volobouev, I; Volpi, G; Würthwein, F; Wagner, P; Wagner, R G; Wagner, R L; Wagner, J; Wagner, W; Wallny, R; Wang, S M; Warburton, A; Waschke, S; Waters, D; Wester, W C; Whitehouse, B; Whiteson, D; Wicklund, A B; Wicklund, E; Williams, G; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, C; Wright, T; Wu, X; Wynne, S M; Yagil, A; Yamamoto, K; Yamaoka, J; Yamashita, T; Yang, C; Yang, U K; Yang, Y C; Yao, W M; Yeh, G P; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanello, L; Zanetti, A; Zaw, I; Zhang, X; Zhou, J; Zucchelli, S

2007-03-23

We present the first observation of the baryon decay Lambda b0-->Lambda c+pi- followed by Lambda c+-->pK-pi+ in 106 pb-1 pp collisions at square root s=1.96 TeV in the CDF experiment. In order to reduce systematic error, the measured rate for Lambda b0 decay is normalized to the kinematically similar meson decay B0-->D+pi- followed by D+-->pi+K-pi+. We report the ratio of production cross sections (sigma) times the ratio of branching fractions (B) for the momentum region integrated above pT>6 GeV/c and pseudorapidity range |eta|<1.3: sigma(pp-->Lambda b0X)/sigma(pp-->B0X)xB(Lambda b0-->Lambda c+pi-)/B(B0-->D+pi-)=0.82+/-0.08(stat)+/-0.11(syst)+/-0.22[B(Lambda c+-->pK-pi+)].

Engineering-scale experiments of solar photocatalytic oxidation of trichloroethylene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pacheco, J.; Prairie, M.; Evans, L.

1990-01-01

A photocatalytic process is being developed to destroy organic contaminants in water. Tests with a common water pollutant, trichlorethylene (TCE), were conducted at the Solar Thermal Test Facility at Sandia with trough systems. Tests at this scale provide verification of laboratory studies and allow examination of design and operation issues that only arise in experiments on a realistic scale. The catalyst, titanium dioxide (TiO{sub 2}), is a harmless material found in paint, cosmetics and even toothpaste. We examined the effect of initial contaminant concentration and the effect of hydrogen peroxide on the photocatalytic decomposition of trichlorethylene (TCE). An aqueous solutionmore » of 5000 parts per billion (ppB) TCE with 0.1 weight {percent} suspended titanium dioxide catalyst required approximately 4.2 minutes of exposure to destroy the TCE to a detection limit of 5 ppB. For a 300 ppB TCE solution, the time required was only 2.5 minutes to reach the same level of destruction. Adding 250 parts per million (ppM) of hydrogen peroxide reduced the time required by about 1 minute. A two parameter Langmuir Hinshelwood model was able to describe the data. A simple flow apparatus was built to test four fixed catalyst supports and to measure their pressure drop and assess their ability to withstand flow conditions typical of a full-sized system. In this paper, we summarize the engineering-scale testing and results. 16 refs., 5 figs.« less

Influence of non-thermal TiCl4/Ar+O2 plasma-assisted TiOx based coatings on the surface of polypropylene (PP) films for the tailoring of surface properties and cytocompatibility.

PubMed

Pandiyaraj, K N; Kumar, A Arun; Ramkumar, M C; Sachdev, A; Gopinath, P; Cools, Pieter; De Geyter, N; Morent, R; Deshmukh, R R; Hegde, P; Han, C; Nadagouda, M N

2016-05-01

The superior bulk properties (corrosion resistance, high strength to weight ratio, relatively low cost and easy processing) of hydrocarbon based polymers such as polypropylene (PP) have contributed significantly to the development of new biomedical applications such as artificial organs and cell scaffolds. However, low cell affinity is one of the main draw backs for PP due to its poor surface properties. In tissue engineering, physico-chemical surface properties such as hydrophilicity, polar functional groups, surface charge and morphology play a crucial role to enrich the cell proliferation and adhesion. In this present investigation TiOx based biocompatible coatings were developed on the surface of PP films via DC excited glow discharge plasma, using TiCl4/Ar+O2 gas mixture as a precursor. Various TiOx-based coatings are deposited on the surface of PP films as a function of discharge power. The changes in hydrophilicity of the TiOx/PP film surfaces were studied using contact angle analysis and surface energy calculations by Fowke's approximation. X-ray photo-electron spectroscopy (XPS) was used to investigate the surface chemical composition of TiOx/PP films. The surface morphology of the obtained TiOx/PP films was investigated by scanning electron and transmission electron microscopy (SEM &TEM). Moreover, the surface topography of the material was analyzed by atomic force microscopy (AFM). The cytocompatibility of the TiOx/PP films was investigated via in vitro analysis (cell viability, adhesion and cytotoxicity) using NIH3T3 (mouse embryonic fibroblast) cells. Furthermore the antibacterial activities of TiOx/PP films were also evaluated against two distinct bacterial models namely Gram positive Staphylococcus aureus (S.aureus) and Gram negative Escherichia coli DH5α. (E.coli) bacteria. XPS results clearly indicate the successful incorporation of TiOx and oxygen containing polar functional groups on the surface of plasma treated PP films. Moreover the surface of modified PP films exhibited nano structured morphology, as confirmed by SEM, TEM and AFM. The physico-chemical changes have improved the hydrophilicity of the PP films. The in-vitro analysis clearly confirms that the TiOx coated PP films performs as good as the standard tissue culture plates and also are unlikely to impact the bacterial cell viability. Copyright © 2016 Elsevier B.V. All rights reserved.

Patient derived mutation W257G of PPP2R1A enhances cancer cell migration through SRC-JNK-c-Jun pathway

PubMed Central

Jeong, Ae Lee; Han, Sora; Lee, Sunyi; Su Park, Jeong; Lu, Yiling; Yu, Shuangxing; Li, Jane; Chun, Kyung-Hee; Mills, Gordon B.; Yang, Young

2016-01-01

Mutation of PPP2R1A has been observed at high frequency in endometrial serous carcinomas but at low frequency in ovarian clear cell carcinoma. However, the biological role of mutation of PPP2R1A in ovarian and endometrial cancer progression remains unclear. In this study, we found that PPP2R1A expression is elevated in high-grade primary tumor patients with papillary serous tumors of the ovary. To determine whether increased levels or mutation of PPP2R1A might contribute to cancer progression, the effects of overexpression or mutation of PPP2R1A on cell proliferation, migration, and PP2A phosphatase activity were investigated using ovarian and endometrial cancer cell lines. Among the mutations, PPP2R1A-W257G enhanced cell migration in vitro through activating SRC-JNK-c-Jun pathway. Overexpression of wild type (WT) PPP2R1A increased its binding ability with B56 regulatory subunits, whereas PPP2R1A-mutations lost the ability to bind to most B56 subunits except B56δ. Total PP2A activity and PPP2R1A-associated PP2Ac activity were significantly increased in cells overexpressing PPP2R1A-WT. In addition, overexpression of PPP2R1A-WT increased cell proliferation in vitro and tumor growth in vivo. PMID:27272709

Src family kinases mediate the inhibition of substance P release in the rat spinal cord by μ-opioid receptors and GABAB receptors, but not α2 adrenergic receptors

PubMed Central

Zhang, Guohua; Chen, Wenling; Marvizón, Juan Carlos G.

2010-01-01

GABAB, μ-opioid, and adrenergic α2 receptors inhibit substance P release from primary afferent terminals in the dorsal horn. Studies in cell expression systems suggest that μ-opioid and GABAB receptors inhibit transmitter release from primary afferents by activating Src family kinases (SFKs), which then phosphorylate and inhibit voltage-gated calcium channels. This study investigated whether SFKs mediate the inhibition of substance P release by these three receptors. Substance P release was measured as neurokinin 1 receptor (NK1R) internalization in spinal cord slices and in vivo. In slices, NK1R internalization induced by high frequency dorsal root stimulation was inhibited by the μ-opioid agonist DAMGO and the GABAB agonist baclofen. This inhibition was reversed by the SFK inhibitor PP1. NK1R internalization induced by low frequency stimulation was also inhibited by DAMGO, but PP1 did not reverse this effect. In vivo, NK1R internalization induced by noxious mechanical stimulation of the hind paw was inhibited by intrathecal DAMGO and baclofen. This inhibition was reversed by intrathecal PP1, but not by the inactive PP1 analog PP3. PP1 produced no effect by itself. The α2 adrenergic agonists medetomidine and guanfacine produced a small but statistically significant inhibition of NK1R internalization induced by low frequency dorsal root stimulation. PP1 did not reverse the inhibition by guanfacine. These results show that SFKs mediate the inhibition of substance P release by μ-opioid and GABAB receptors, but not by α2 receptors, which is probably mediated by the binding of G protein βγ subunits to calcium channels. PMID:20726886

Effects of protease, phytase and a Bacillus sp. direct-fed microbial on nutrient and energy digestibility, ileal brush border digestive enzyme activity and cecal short-chain fatty acid concentration in broiler chickens.

PubMed

Murugesan, Ganapathi R; Romero, Luis F; Persia, Michael E

2014-01-01

Two experiments were conducted to determine the effects of protease and phytase (PP) and a Bacillus sp. direct-fed microbial (DFM) on dietary energy and nutrient utilization in broiler chickens. In the first experiment, Ross 308 broiler chicks were fed diets supplemented with PP and DFM in a 2×2 factorial arrangement. The 4 diets (control (CON), CON + PP, CON + DFM, and CON + PP + DFM) were fed from 15-21 days of age. In Experiment 1, significant interaction (P≤0.01) between PP and DFM on the apparent ileal digestibility coefficient for starch, crude protein, and amino acid indicated that both additives increased the digestibility. Both additives increased the nitrogen retention coefficient with a significant interaction (P≤0.01). Although no interaction was observed, significant main effects (P≤0.01) for nitrogen-corrected apparent ME (AMEn) for PP or DFM indicated an additive response. In a follow-up experiment, Ross 308 broiler chicks were fed the same experimental diets from 1-21 days of age. Activities of ileal brush border maltase, sucrase, and L-alanine aminopeptidase were increased (P≤0.01) by PP addition, while a trend (P = 0.07) for increased sucrase activity was observed in chickens fed DFM, in Experiment 2. The proportion of cecal butyrate was increased (P≤0.01) by DFM addition. Increased nutrient utilization and nitrogen retention appear to involve separate but complementary mechanisms for PP and DFM, however AMEn responses appear to have separate and additive mechanisms.

Memantine Attenuates Alzheimer’s Disease-Like Pathology and Cognitive Impairment

PubMed Central

Wang, Xiaochuan; Blanchard, Julie; Iqbal, Khalid

2015-01-01

Deficiency of protein phosphatase-2A is a key event in Alzheimer’s disease. An endogenous inhibitor of protein phosphatase-2A, inhibitor-1, I1 PP2A, which inhibits the phosphatase activity by interacting with its catalytic subunit protein phosphatase-2Ac, is known to be upregulated in Alzheimer’s disease brain. In the present study, we overexpressed I1 PP2A by intracerebroventricular injection with adeno-associated virus vector-1-I1 PP2A in Wistar rats. The I1 PP2A rats showed a decrease in brain protein phosphatase-2A activity, abnormal hyperphosphorylation of tau, neurodegeneration, an increase in the level of activated glycogen synthase kinase-3beta, enhanced expression of intraneuronal amyloid-beta and spatial reference memory deficit; littermates treated identically but with vector only, i.e., adeno-associated virus vector-1-enhanced GFP, served as a control. Treatment with memantine, a noncompetitive NMDA receptor antagonist which is an approved drug for treatment of Alzheimer’s disease, rescued protein phosphatase-2A activity by decreasing its demethylation at Leu309 selectively and attenuated Alzheimer’s disease-like pathology and cognitive impairment in adeno-associated virus vector-1-I1 PP2A rats. These findings provide new clues into the possible mechanism of the beneficial therapeutic effect of memantine in Alzheimer’s disease patients. PMID:26697860

Measurements of inclusive W and Z cross sections in pp collisions at sqrt {s} = 7 TeV

NASA Astrophysics Data System (ADS)

Khachatryan, V.; Sirunyan, A. M.; Tumasyan, A.; Adam, W.; Bergauer, T.; Dragicevic, M.; Erö, J.; Fabjan, C.; Friedl, M.; Frühwirth, R.; Hammer, V. M.; Hammer, J.; Hänsel, S.; Hartl, C.; Hoch, M.; Hörmann, N.; Hrubec, J.; Jeitler, M.; Kasieczka, G.; Kiesenhofer, W.; Krammer, M.; Liko, D.; Mikulec, I.; Pernicka, M.; Rohringer, H.; Schöfbeck, R.; Strauss, J.; Taurok, A.; Teischinger, F.; Waltenberger, W.; Walzel, G.; Widl, E.; Wulz, C.-E.; Mossolov, V.; Shumeiko, N.; Suarez Gonzalez, J.; Benucci, L.; Ceard, L.; Cerny, K.; De Wolf, E. A.; Janssen, X.; Maes, T.; Mucibello, L.; Ochesanu, S.; Roland, B.; Rougny, R.; Selvaggi, M.; Van Haevermaet, H.; Van Mechelen, P.; Van Remortel, N.; Adler, V.; Beauceron, S.; Blekman, F.; Blyweert, S.; D'Hondt, J.; Devroede, O.; Kalogeropoulos, A.; Maes, J.; Maes, M.; Tavernier, S.; Van Doninck, W.; Van Mulders, P.; Van Onsem, G. P.; Villella, I.; Charaf, O.; Clerbaux, B.; De Lentdecker, G.; Dero, V.; Gay, A. P. R.; Hammad, G. H.; Hreus, T.; Marage, P. E.; Thomas, L.; Vander Velde, C.; Vanlaer, P.; Wickens, J.; Costantini, S.; Grunewald, M.; Klein, B.; Marinov, A.; Ryckbosch, D.; Thyssen, F.; Tytgat, M.; Vanelderen, L.; Verwilligen, P.; Walsh, S.; Zaganidis, N.; Basegmez, S.; Bruno, G.; Caudron, J.; De Favereau De Jeneret, J.; Delaere, C.; Demin, P.; Favart, D.; Giammanco, A.; Grégoire, G.; Hollar, J.; Lemaitre, V.; Liao, J.; Militaru, O.; Ovyn, S.; Pagano, D.; Pin, A.; Piotrzkowski, K.; Quertenmont, L.; Schul, N.; Beliy, N.; Caebergs, T.; Daubie, E.; Alves, G. A.; De Jesus Damiao, D.; Pol, M. E.; Souza, M. H. G.; Carvalho, W.; Da Costa, E. M.; De Oliveira Martins, C.; De Souza, S. Fonseca; Mundim, L.; Nogima, H.; Oguri, V.; Da Silva, W. L. Prado; Santoro, A.; Silva Do Amaral, S. M.; Sznajder, A.; Torres Da Silva De Araujo, F.; Dias, F. A.; Dias, M. A. F.; Fernandez Perez Tomei, T. R.; Gregores, E. M.; Marinho, F.; Novaes, S. F.; Padula, S. S.; Darmenov, N.; Dimitrov, L.; Genchev, V.; Iaydjiev, P.; Piperov, S.; Rodozov, M.; Stoykova, S.; Sultanov, G.; Tcholakov, V.; Trayanov, R.; Vankov, I.; Dyulendarova, M.; Hadjiiska, R.; Kozhuharov, V.; Litov, L.; Marinova, E.; Mateev, M.; Pavlov, B.; Petkov, P.; Bian, J. G.; Chen, G. M.; Chen, H. S.; Jiang, C. H.; Liang, D.; Liang, S.; Wang, J.; Wang, J.; Wang, X.; Wang, Z.; Yang, M.; Zang, J.; Zhang, Z.; Ban, Y.; Guo, S.; Li, W.; Mao, Y.; Qian, S. J.; Teng, H.; Zhu, B.; Cabrera, A.; Gomez Moreno, B.; Ocampo Rios, A. A.; Osorio Oliveros, A. F.; Sanabria, J. C.; Godinovic, N.; Lelas, D.; Lelas, K.; Plestina, R.; Polic, D.; Puljak, I.; Antunovic, Z.; Dzelalija, M.; Brigljevic, V.; Duric, S.; Kadija, K.; Morovic, S.; Attikis, A.; Fereos, R.; Galanti, M.; Mousa, J.; Nicolaou, C.; Ptochos, F.; Razis, P. A.; Rykaczewski, H.; Assran, Y.; Mahmoud, M. A.; Hektor, A.; Kadastik, M.; Kannike, K.; Müntel, M.; Raidal, M.; Rebane, L.; Azzolini, V.; Eerola, P.; Czellar, S.; Härkönen, J.; Heikkinen, A.; Karimäki, V.; Kinnunen, R.; Klem, J.; Kortelainen, M. J.; Lampén, T.; Lassila-Perini, K.; Lehti, S.; Lindén, T.; Luukka, P.; Mäenpää, T.; Tuominen, E.; Tuominiemi, J.; Tuovinen, E.; Ungaro, D.; Wendland, L.; Banzuzi, K.; Korpela, A.; Tuuva, T.; Sillou, D.; Besancon, M.; Dejardin, M.; Denegri, D.; Fabbro, B.; Faure, J. L.; Ferri, F.; Ganjour, S.; Gentit, F. X.; Givernaud, A.; Gras, P.; de Monchenault, G. Hamel; Jarry, P.; Locci, E.; Malcles, J.; Marionneau, M.; Millischer, L.; Rander, J.; Rosowsky, A.; Shreyber, I.; Titov, M.; Verrecchia, P.; Baffioni, S.; Beaudette, F.; Bianchini, L.; Bluj, M.; Broutin, C.; Busson, P.; Charlot, C.; Dobrzynski, L.; de Cassagnac, R. Granier; Haguenauer, M.; Miné, P.; Mironov, C.; Ochando, C.; Paganini, P.; Sabes, S. Porteboeuf, D.; Salerno, R.; Sirois, Y.; Thiebaux, C.; Wyslouch, B.; Zabi, A.; Agram, J.-L.; Andrea, J.; Besson, A.; Bloch, D.; Bodin, D.; Brom, J.-M.; Cardaci, M.; Chabert, E. C.; Collard, C.; Conte, E.; Drouhin, F.; Ferro, C.; Fontaine, J.-C.; Gelé, D.; Goerlach, U.; Greder, S.; Juillot, P.; Karim, M.; Le Bihan, A.-C.; Mikami, Y.; Van Hove, P.; Fassi, F.; Mercier, D.; Baty, C.; Beaupere, N.; Bedjidian, M.; Bondu, O.; Boudoul, G.; Boumediene, D.; Brun, H.; Chanon, N.; Chierici, R.; Contardo, D.; Depasse, P.; El Mamouni, H.; Falkiewicz, A.; Fay, J.; Gascon, S.; Ille, B.; Kurca, T.; Le Grand, T.; Lethuillier, M.; Mirabito, L.; Perries, S.; Sordini, V.; Tosi, S.; Tschudi, Y.; Verdier, P.; Xiao, H.; Roinishvili, V.; Anagnostou, G.; Edelhoff, M.; Feld, L.; Heracleous, N.; Hindrichs, O.; Jussen, R.; Klein, K.; Merz, J.; Mohr, N.; Ostapchuk, A.; Perieanu, A.; Raupach, F.; Sammet, J.; Schael, S.; Sprenger, D.; Weber, H.; Weber, M.; Wittmer, B.; Ata, M.; Bender, W.; Erdmann, M.; Frangenheim, J.; Hebbeker, T.; Hinzmann, A.; Hoepfner, K.; Hof, C.; Klimkovich, T.; Klingebiel, D.; Kreuzer, P.; Lanske, D.; Magass, C.; Masetti, G.; Merschmeyer, M.; Meyer, A.; Papacz, P.; Pieta, H.; Reithler, H.; Schmitz, S. A.; Sonnenschein, L.; Steggemann, J.; Teyssier, D.; Bontenackels, M.; Davids, M.; Duda, M.; Flügge, G.; Geenen, H.; Giffels, M.; Haj Ahmad, W.; Heydhausen, D.; Kress, T.; Kuessel, Y.; Linn, A.; Nowack, A.; Perchalla, L.; Pooth, O.; Rennefeld, J.; Sauerland, P.; Stahl, A.; Thomas, M.; Tornier, D.; Zoeller, M. H.; Aldaya Martin, M.; Behrenhoff, W.; Behrens, U.; Bergholz, M.; Borras, K.; Cakir, A.; Campbell, A.; Castro, E.; Dammann, D.; Eckerlin, G.; Eckstein, D.; Flossdorf, A.; Flucke, G.; Geiser, A.; Glushkov, I.; Hauk, J.; Jung, H.; Kasemann, M.; Katkov, I.; Katsas, P.; Kleinwort, C.; Kluge, H.; Knutsson, A.; Krücker, D.; Kuznetsova, E.; Lange, W.; Lohmann, W.; Mankel, R.; Marienfeld, M.; Melzer-Pellmann, I.-A.; Meyer, A. B.; Mnich, J.; Mussgiller, A.; Olzem, J.; Parenti, A.; Raspereza, A.; Raval, A.; Schmidt, R.; Schoerner-Sadenius, T.; Sen, N.; Stein, M.; Tomaszewska, J.; Volyanskyy, D.; Walsh, R.; Wissing, C.; Autermann, C.; Bobrovskyi, S.; Draeger, J.; Enderle, H.; Gebbert, U.; Kaschube, K.; Kaussen, G.; Klanner, R.; Mura, B.; Naumann-Emme, S.; Nowak, F.; Pietsch, N.; Sander, C.; Schettler, H.; Schleper, P.; Schröder, M.; Schum, T.; Schwandt, J.; Srivastava, A. K.; Stadie, H.; Steinbrück, G.; Thomsen, J.; Wolf, R.; Bauer, J.; Buege, V.; Chwalek, T.; De Boer, W.; Dierlamm, A.; Dirkes, G.; Feindt, M.; Gruschke, J.; Hackstein, C.; Hartmann, F.; Heindl, S. M.; Heinrich, M.; Held, H.; Hoffmann, K. H.; Honc, S.; Kuhr, T.; Martschei, D.; Mueller, S.; Müller, Th.; Niegel, M.; Oberst, O.; Oehler, A.; Ott, J.; Peiffer, T.; Piparo, D.; Quast, G.; Rabbertz, K.; Ratnikov, F.; Renz, M.; Saout, C.; Scheurer, A.; Schieferdecker, P.; Schilling, F.-P.; Schott, G.; Simonis, H. J.; Stober, F. M.; Troendle, D.; Wagner-Kuhr, J.; Zeise, M.; Zhukov, V.; Ziebarth, E. B.; Daskalakis, G.; Geralis, T.; Kesisoglou, S.; Kyriakis, A.; Loukas, D.; Manolakos, I.; Markou, A.; Markou, C.; Mavrommatis, C.; Petrakou, E.; Gouskos, L.; Mertzimekis, T. J.; Panagiotou, A.; Evangelou, I.; Foudas, C.; Kokkas, P.; Manthos, N.; Papadopoulos, I.; Patras, V.; Triantis, F. A.; Aranyi, A.; Bencze, G.; Boldizsar, L.; Debreczeni, G.; Hajdu, C.; Horvath, D.; Kapusi, A.; Krajczar, K.; Laszlo, A.; Sikler, F.; Vesztergombi, G.; Beni, N.; Molnar, J.; Palinkas, J.; Szillasi, Z.; Veszpremi, V.; Raics, P.; Trocsanyi, Z. L.; Ujvari, B.; Bansal, S.; Beri, S. B.; Bhatnagar, V.; Dhingra, N.; Jindal, M.; Kaur, M.; Kohli, J. M.; Mehta, M. Z.; Nishu, N.; Saini, L. K.; Sharma, A.; Singh, A. P.; Singh, J. B.; Singh, S. P.; Ahuja, S.; Bhattacharya, S.; Choudhary, B. C.; Gupta, P.; Jain, S.; Jain, S.; Kumar, A.; Shivpuri, R. K.; Choudhury, R. K.; Dutta, D.; Kailas, S.; Kataria, S. K.; Mohanty, A. K.; Pant, L. M.; Shukla, P.; Suggisetti, P.; Aziz, T.; Guchait, M.; Gurtu, A.; Maity, M.; Majumder, D.; Majumder, G.; Mazumdar, K.; Mohanty, G. B.; Saha, A.; Sudhakar, K.; Wickramage, N.; Banerjee, S.; Dugad, S.; Mondal, N. K.; Arfaei, H.; Bakhshiansohi, H.; Etesami, S. M.; Fahim, A.; Hashemi, M.; Jafari, A.; Khakzad, M.; Mohammadi, A.; Mohammadi Najafabadi, M.; Paktinat Mehdiabadi, S.; Safarzadeh, B.; Zeinali, M.; Abbrescia, M.; Barbone, L.; Calabria, C.; Colaleo, A.; Creanza, D.; De Filippis, N.; De Palma, M.; Dimitrov, A.; Fedele, F.; Fiore, L.; Iaselli, G.; Lusito, L.; Maggi, G.; Maggi, M.; Manna, N.; Marangelli, B.; My, S.; Nuzzo, S.; Pacifico, N.; Pierro, G. A.; Pompili, A.; Pugliese, G.; Romano, F.; Roselli, G.; Selvaggi, G.; Silvestris, L.; Trentadue, R.; Tupputi, S.; Zito, G.; Abbiendi, G.; Benvenuti, A. C.; Bonacorsi, D.; Braibant-Giacomelli, S.; Capiluppi, P.; Castro, A.; Cavallo, F. R.; Cuffiani, M.; Dallavalle, G. M.; Fabbri, F.; Fanfani, A.; Fasanella, D.; Giacomelli, P.; Giunta, M.; Grandi, C.; Marcellini, S.; Meneghelli, M.; Montanari, A.; Navarria, F. L.; Odorici, F.; Perrotta, A.; Rossi, A. M.; Rovelli, T.; Siroli, G.; Travaglini, R.; Albergo, S.; Cappello, G.; Chiorboli, M.; Costa, S.; Tricomi, A.; Tuve, C.; Barbagli, G.; Ciulli, V.; Civinini, C.; D'Alessandro, R.; Focardi, E.; Frosali, S.; Gallo, E.; Genta, C.; Lenzi, P.; Meschini, M.; Paoletti, S.; Sguazzoni, G.; Tropiano, A.; Benussi, L.; Bianco, S.; Colafranceschi, S.; Fabbri, F.; Piccolo, D.; Fabbricatore, P.; Musenich, R.; Benaglia, A.; Cerati, G. B.; De Guio, F.; Di Matteo, L.; Ghezzi, A.; Malberti, M.; Malvezzi, S.; Martelli, A.; Massironi, A.; Menasce, D.; Moroni, L.; Paganoni, M.; Pedrini, D.; Ragazzi, S.; Redaelli, N.; Sala, S.; de Fatis, T. Tabarelli; Tancini, V.; Buontempo, S.; Carrillo Montoya, C. A.; Cimmino, A.; De Cosa, A.; De Gruttola, M.; Fabozzi, F.; Iorio, A. O. M.; Lista, L.; Merola, M.; Noli, P.; Paolucci, P.; Azzi, P.; Bacchetta, N.; Bellan, P.; Biasotto, M.; Bisello, D.; Branca, A.; Carlin, R.; Checchia, P.; Conti, E.; De Mattia, M.; Dorigo, T.; Fanzago, F.; Gasparini, F.; Giubilato, P.; Gresele, A.; Lacaprara, S.; Lazzizzera, I.; Margoni, M.; Meneguzzo, A. T.; Nespolo, M.; Perrozzi, L.; Pozzobon, N.; Ronchese, P.; Simonetto, F.; Torassa, E.; Tosi, M.; Vanini, S.; Ventura, S.; Zotto, P.; Zumerle, G.; Baesso, P.; Berzano, U.; Riccardi, C.; Torre, P.; Vitulo, P.; Viviani, C.; Biasini, M.; Bilei, G. M.; Caponeri, B.; Fanò, L.; Lariccia, P.; Lucaroni, A.; Mantovani, G.; Menichelli, M.; Nappi, A.; Santocchia, A.; Servoli, L.; Taroni, S.; Valdata, M.; Volpe, R.; Azzurri, P.; Bagliesi, G.; Bernardini, J.; Boccali, T.; Broccolo, G.; Castaldi, R.; D'Agnolo, R. T.; Dell'Orso, R.; Fiori, F.; Foà, L.; Giassi, A.; Kraan, A.; Ligabue, F.; Lomtadze, T.; Martini, L.; Messineo, A.; Palla, F.; Palmonari, F.; Sarkar, S.; Segneri, G.; Serban, A. T.; Spagnolo, P.; Tenchini, R.; Tonelli, G.; Venturi, A.; Verdini, P. G.; Barone, L.; Cavallari, F.; Del Re, D.; Di Marco, E.; Diemoz, M.; Franci, D.; Grassi, M.; Longo, E.; Organtini, G.; Palma, A.; Pandolfi, F.; Paramatti, R.; Rahatlou, S.; Amapane, N.; Arcidiacono, R.; Argiro, S.; Arneodo, M.; Biino, C.; Botta, C.; Cartiglia, N.; Castello, R.; Costa, M.; Demaria, N.; Graziano, A.; Mariotti, C.; Marone, M.; Maselli, S.; Migliore, E.; Mila, G.; Monaco, V.; Musich, M.; Obertino, M. M.; Pastrone, N.; Pelliccioni, M.; Romero, A.; Ruspa, M.; Sacchi, R.; Sola, V.; Solano, A.; Staiano, A.; Trocino, D.; Vilela Pereira, A.; Ambroglini, F.; Belforte, S.; Cossutti, F.; Della Ricca, G.; Gobbo, B.; Montanino, D.; Penzo, A.; Heo, S. G.; Chang, S.; Chung, J.; Kim, D. H.; Kim, G. N.; Kim, J. E.; Kong, D. J.; Park, H.; Son, D.; Son, D. C.; Kim, Zero; Kim, J. Y.; Song, S.; Choi, S.; Hong, B.; Jo, M.; Kim, H.; Kim, J. H.; Kim, T. J.; Lee, K. S.; Moon, D. H.; Park, S. K.; Rhee, H. B.; Seo, E.; Shin, S.; Sim, K. S.; Choi, M.; Kang, S.; Kim, H.; Park, C.; Park, I. C.; Park, S.; Ryu, G.; Choi, Y.; Choi, Y. K.; Goh, J.; Lee, J.; Lee, S.; Seo, H.; Yu, I.; Bilinskas, M. J.; Grigelionis, I.; Janulis, M.; Martisiute, D.; Petrov, P.; Sabonis, T.; Castilla Valdez, H.; De La Cruz Burelo, E.; Lopez-Fernandez, R.; Sánchez Hernández, A.; Villasenor-Cendejas, L. M.; Carrillo Moreno, S.; Vazquez Valencia, F.; Salazar Ibarguen, H. A.; Casimiro Linares, E.; Morelos Pineda, A.; Reyes-Santos, M. A.; Allfrey, P.; Krofcheck, D.; Tam, J.; Butler, P. H.; Doesburg, R.; Silverwood, H.; Ahmad, M.; Ahmed, I.; Asghar, M. I.; Hoorani, H. R.; Khan, W. A.; Khurshid, T.; Qazi, S.; Cwiok, M.; Dominik, W.; Doroba, K.; Kalinowski, A.; Konecki, M.; Krolikowski, J.; Frueboes, T.; Gokieli, R.; Górski, M.; Kazana, M.; Nawrocki, K.; Romanowska-Rybinska, K.; Szleper, M.; Wrochna, G.; Zalewski, P.; Almeida, N.; David, A.; Faccioli, P.; Ferreira Parracho, P. G.; Gallinaro, M.; Martins, P.; Musella, P.; Nayak, A.; Ribeiro, P. Q.; Seixas, J.; Silva, P.; Varela, J.; Wöhri, H. K.; Belotelov, I.; Bunin, P.; Finger, M.; Finger, M.; Golutvin, I.; Kamenev, A.; Karjavin, V.; Kozlov, G.; Lanev, A.; Moisenz, P.; Palichik, V.; Perelygin, V.; Shmatov, S.; Smirnov, V.; Volodko, A.; Zarubin, A.; Bondar, N.; Golovtsov, V.; Ivanov, Y.; Kim, V.; Levchenko, P.; Murzin, V.; Oreshkin, V.; Smirnov, I.; Sulimov, V.; Uvarov, L.; Vavilov, S.; Vorobyev, A.; Andreev, Yu.; Gninenko, S.; Golubev, N.; Kirsanov, M.; Krasnikov, N.; Matveev, V.; Pashenkov, A.; Toropin, A.; Troitsky, S.; Epshteyn, V.; Gavrilov, V.; Kaftanov, V.; Kossov, M.; Krokhotin, A.; Lychkovskaya, N.; Safronov, G.; Semenov, S.; Stolin, V.; Vlasov, E.; Zhokin, A.; Boos, E.; Dubinin, M.; Dudko, L.; Ershov, A.; Gribushin, A.; Kodolova, O.; Lokhtin, I.; Obraztsov, S.; Petrushanko, S.; Sarycheva, L.; Savrin, V.; Snigirev, A.; Andreev, V.; Azarkin, M.; Dremin, I.; Kirakosyan, M.; Rusakov, S. V.; Vinogradov, A.; Azhgirey, I.; Bitioukov, S.; Grishin, V.; Kachanov, V.; Konstantinov, D.; Korablev, A.; Krychkine, V.; Petrov, V.; Ryutin, R.; Slabospitsky, S.; Sobol, A.; Tourtchanovitch, L.; Troshin, S.; Tyurin, N.; Uzunian, A.; Volkov, A.; Adzic, P.; Djordjevic, M.; Krpic, D.; Milosevic, J.; Aguilar-Benitez, M.; Alcaraz Maestre, J.; Arce, P.; Battilana, C.; Calvo, E.; Cepeda, M.; Cerrada, M.; Colino, N.; De La Cruz, B.; Diez Pardos, C.; Fernandez Bedoya, C.; Fernández Ramos, J. P.; Ferrando, A.; Flix, J.; Fouz, M. C.; Garcia-Abia, P.; Gonzalez Lopez, O.; Goy Lopez, S.; Hernandez, J. M.; Josa, M. I.; Merino, G.; Puerta Pelayo, J.; Redondo, I.; Romero, L.; Santaolalla, J.; Willmott, C.; Albajar, C.; Codispoti, G.; de Trocóniz, J. F.; Cuevas, J.; Fernandez Menendez, J.; Folgueras, S.; Gonzalez Caballero, I.; Lloret Iglesias, L.; Vizan Garcia, J. M.; Brochero Cifuentes, J. A.; Cabrillo, I. J.; Calderon, A.; Chamizo Llatas, M.; Chuang, S. H.; Duarte Campderros, J.; Felcini, M.; Fernandez, M.; Gomez, G.; Gonzalez Sanchez, J.; Gonzalez Suarez, R.; Jorda, C.; Lobelle Pardo, P.; Lopez Virto, A.; Marco, J.; Marco, R.; Martinez Rivero, C.; Matorras, F.; Munoz Sanchez, F. J.; Piedra Gomez, J.; Rodrigo, T.; Ruiz Jimeno, A.; Scodellaro, L.; Sobron Sanudo, M.; Vila, I.; Vilar Cortabitarte, R.; Abbaneo, D.; Auffray, E.; Auzinger, G.; Baillon, P.; Ball, A. H.; Barney, D.; Bell, A. J.; Benedetti, D.; Bernet, C.; Bialas, W.; Bloch, P.; Bocci, A.; Bolognesi, S.; Breuker, H.; Brona, G.; Bunkowski, K.; Camporesi, T.; Cano, E.; Cerminara, G.; Christiansen, T.; Coarasa Perez, J. A.; Covarelli, R.; Curé, B.; D'Enterria, D.; Dahms, T.; De Roeck, A.; Duarte Ramos, F.; Elliott-Peisert, A.; Funk, W.; Gaddi, A.; Gennai, S.; Georgiou, G.; Gerwig, H.; Gigi, D.; Gill, K.; Giordano, D.; Glege, F.; Gomez-Reino Garrido, R.; Gouzevitch, M.; Govoni, P.; Gowdy, S.; Guiducci, L.; Hansen, M.; Harvey, J.; Hegeman, J.; Hegner, B.; Henderson, C.; Hoffmann, H. F.; Honma, A.; Innocente, V.; Janot, P.; Karavakis, E.; Lecoq, P.; Leonidopoulos, C.; Lourenço, C.; Macpherson, A.; Mäki, T.; Malgeri, L.; Mannelli, M.; Masetti, L.; Meijers, F.; Mersi, S.; Meschi, E.; Moser, R.; Mozer, M. U.; Mulders, M.; Nesvold, E.; Nguyen, M.; Orimoto, T.; Orsini, L.; Perez, E.; Petrilli, A.; Pfeiffer, A.; Pierini, M.; Pimiä, M.; Polese, G.; Racz, A.; Rolandi, G.; Rommerskirchen, T.; Rovelli, C.; Rovere, M.; Sakulin, H.; Schäfer, C.; Schwick, C.; Segoni, I.; Sharma, A.; Siegrist, P.; Simon, M.; Sphicas, P.; Spiga, D.; Spiropulu, M.; Stöckli, F.; Stoye, M.; Tropea, P.; Tsirou, A.; Tsyganov, A.; Veres, G. I.; Vichoudis, P.; Voutilainen, M.; Zeuner, W. D.; Bertl, W.; Deiters, K.; Erdmann, W.; Gabathuler, K.; Horisberger, R.; Ingram, Q.; Kaestli, H. C.; König, S.; Kotlinski, D.; Langenegger, U.; Meier, F.; Renker, D.; Rohe, T.; Sibille, J.; Starodumov, A.; Bortignon, P.; Caminada, L.; Chen, Z.; Cittolin, S.; Dissertori, G.; Dittmar, M.; Eugster, J.; Freudenreich, K.; Grab, C.; Hervé, A.; Hintz, W.; Lecomte, P.; Lustermann, W.; Marchica, C.; del Arbol, P. Martinez Ruiz; Meridiani, P.; Milenovic, P.; Moortgat, F.; Nef, P.; Nessi-Tedaldi, F.; Pape, L.; Pauss, F.; Punz, T.; Rizzi, A.; Ronga, F. J.; Sala, L.; Sanchez, A. K.; Sawley, M. C.; Stieger, B.; Tauscher, L.; Thea, A.; Theofilatos, K.; Treille, D.; Urscheler, C.; Wallny, R.; Weber, M.; Wehrli, L.; Weng, J.; Aguiló, E.; Amsler, C.; Chiochia, V.; De Visscher, S.; Favaro, C.; Ivova Rikova, M.; Millan Mejias, B.; Regenfus, C.; Robmann, P.; Schmidt, A.; Snoek, H.; Wilke, L.; Chang, Y. H.; Chen, K. H.; Chen, W. T.; Dutta, S.; Go, A.; Kuo, C. M.; Li, S. W.; Lin, W.; Liu, M. H.; Liu, Z. K.; Lu, Y. J.; Wu, J. H.; Yu, S. S.; Bartalini, P.; Chang, P.; Chang, Y. H.; Chang, Y. W.; Chao, Y.; Chen, K. F.; Hou, W.-S.; Hsiung, Y.; Kao, K. Y.; Lei, Y. J.; Lu, R.-S.; Shiu, J. G.; Tzeng, Y. M.; Wang, M.; Adiguzel, A.; Bakirci, M. N.; Cerci, S.; Dozen, C.; Dumanoglu, I.; Eskut, E.; Girgis, S.; Gökbulut, G.; Güler, Y.; Gurpinar, E.; Hos, I.; Kangal, E. E.; Karaman, T.; Kayis Topaksu, A.; Nart, A.; Önengüt, G.; Ozdemir, K.; Ozturk, S.; Polatöz, A.; Sogut, K.; Tali, B.; Topakli, H.; Uzun, D.; Vergili, L. N.; Vergili, M.; Zorbilmez, C.; Akin, I. V.; Aliev, T.; Bimis, S.; Deniz, M.; Gamsizkan, H.; Guler, A. M.; Ocalan, K.; Ozpineci, A.; Serin, M.; Sever, R.; Surat, U. E.; Yildirim, E.; Zeyrek, M.; Deliomeroglu, M.; Demir, D.; Gülmez, E.; Halu, A.; Isildak, B.; Kaya, M.; Kaya, O.; Özbek, M.; Ozkorucuklu, S.; Sonmez, N.; Levchuk, L.; Bell, P.; Bostock, F.; Brooke, J. J.; Cheng, T. L.; Clement, E.; Cussans, D.; Frazier, R.; Goldstein, J.; Grimes, M.; Hansen, M.; Hartley, D.; Heath, G. P.; Heath, H. F.; Huckvale, B.; Jackson, J.; Kreczko, L.; Metson, S.; Newbold, D. M.; Nirunpong, K.; Poll, A.; Senkin, S.; Smith, V. J.; Ward, S.; Basso, L.; Bell, K. W.; Belyaev, A.; Brew, C.; Brown, R. M.; Camanzi, B.; Cockerill, D. J. A.; Coughlan, J. A.; Harder, K.; Harper, S.; Kennedy, B. W.; Olaiya, E.; Petyt, D.; Radburn-Smith, B. C.; Shepherd-Themistocleous, C. H.; Tomalin, I. R.; Womersley, W. J.; Worm, S. D.; Bainbridge, R.; Ball, G.; Ballin, J.; Beuselinck, R.; Buchmuller, O.; Colling, D.; Cripps, N.; Cutajar, M.; Davies, G.; Della Negra, M.; Fulcher, J.; Futyan, D.; Guneratne Bryer, A.; Hall, G.; Hatherell, Z.; Hays, J.; Iles, G.; Karapostoli, G.; Lyons, L.; Magnan, A.-M.; Marrouche, J.; Nandi, R.; Nash, J.; Nikitenko, A.; Papageorgiou, A.; Pesaresi, M.; Petridis, K.; Pioppi, M.; Raymond, D. M.; Rompotis, N.; Rose, A.; Ryan, M. J.; Seez, C.; Sharp, P.; Sparrow, A.; Tapper, A.; Tourneur, S.; Vazquez Acosta, M.; Virdee, T.; Wakefield, S.; Wardrope, D.; Whyntie, T.; Barrett, M.; Chadwick, M.; Cole, J. E.; Hobson, P. R.; Khan, A.; Kyberd, P.; Leslie, D.; Martin, W.; Reid, I. D.; Teodorescu, L.; Hatakeyama, K.; Bose, T.; Carrera Jarrin, E.; Clough, A.; Fantasia, C.; Heister, A.; John, J. St.; Lawson, P.; Lazic, D.; Rohlf, J.; Sperka, D.; Sulak, L.; Avetisyan, A.; Bhattacharya, S.; Chou, J. P.; Cutts, D.; Esen, S.; Ferapontov, A.; Heintz, U.; Jabeen, S.; Kukartsev, G.; Landsberg, G.; Narain, M.; Nguyen, D.; Segala, M.; Speer, T.; Tsang, K. V.; Borgia, M. A.; Breedon, R.; De La Barca Sanchez, M. Calderon; Cebra, D.; Chauhan, S.; Chertok, M.; Conway, J.; Cox, P. T.; Dolen, J.; Erbacher, R.; Friis, E.; Ko, W.; Kopecky, A.; Lander, R.; Liu, H.; Maruyama, S.; Miceli, T.; Nikolic, M.; Pellett, D.; Robles, J.; Schwarz, T.; Searle, M.; Smith, J.; Squires, M.; Tripathi, M.; Vasquez Sierra, R.; Veelken, C.; Andreev, V.; Arisaka, K.; Cline, D.; Cousins, R.; Deisher, A.; Duris, J.; Erhan, S.; Farrell, C.; Hauser, J.; Ignatenko, M.; Jarvis, C.; Plager, C.; Rakness, G.; Schlein, P.; Tucker, J.; Valuev, V.; Babb, J.; Clare, R.; Ellison, J.; Gary, J. W.; Giordano, F.; Hanson, G.; Jeng, G. Y.; Kao, S. C.; Liu, F.; Liu, H.; Luthra, A.; Nguyen, H.; Pasztor, G.; Satpathy, A.; Shen, B. C.; Stringer, R.; Sturdy, J.; Sumowidagdo, S.; Wilken, R.; Wimpenny, S.; Andrews, W.; Branson, J. G.; Dusinberre, E.; Evans, D.; Golf, F.; Holzner, A.; Kelley, R.; Lebourgeois, M.; Letts, J.; Mangano, B.; Muelmenstaedt, J.; Padhi, S.; Palmer, C.; Petrucciani, G.; Pi, H.; Pieri, M.; Ranieri, R.; Sani, M.; Sharma, V.; Simon, S.; Tu, Y.; Vartak, A.; Würthwein, F.; Yagil, A.; Barge, D.; Bellan, R.; Campagnari, C.; D'Alfonso, M.; Danielson, T.; Geffert, P.; Incandela, J.; Justus, C.; Kalavase, P.; Koay, S. A.; Kovalskyi, D.; Krutelyov, V.; Lowette, S.; Mccoll, N.; Pavlunin, V.; Rebassoo, F.; Ribnik, J.; Richman, J.; Rossin, R.; Stuart, D.; To, W.; Vlimant, J. R.; Bornheim, A.; Bunn, J.; Chen, Y.; Gataullin, M.; Kcira, D.; Litvine, V.; Ma, Y.; Mott, A.; Newman, H. B.; Rogan, C.; Timciuc, V.; Traczyk, P.; Veverka, J.; Wilkinson, R.; Yang, Y.; Zhu, R. Y.; Akgun, B.; Carroll, R.; Ferguson, T.; Iiyama, Y.; Jang, D. W.; Jun, S. Y.; Liu, Y. F.; Paulini, M.; Russ, J.; Terentyev, N.; Vogel, H.; Vorobiev, I.; Cumalat, J. P.; Dinardo, M. E.; Drell, B. R.; Edelmaier, C. J.; Ford, W. T.; Heyburn, B.; Luiggi Lopez, E.; Nauenberg, U.; Smith, J. G.; Stenson, K.; Ulmer, K. A.; Wagner, S. R.; Zang, S. L.; Agostino, L.; Alexander, J.; Chatterjee, A.; Das, S.; Eggert, N.; Fields, L. J.; Gibbons, L. K.; Heltsley, B.; Hopkins, W.; Khukhunaishvili, A.; Kreis, B.; Kuznetsov, V.; Nicolas Kaufman, G.; Patterson, J. R.; Puigh, D.; Riley, D.; Ryd, A.; Shi, X.; Sun, W.; Teo, W. D.; Thom, J.; Thompson, J.; Vaughan, J.; Weng, Y.; Winstrom, L.; Wittich, P.; Biselli, A.; Cirino, G.; Winn, D.; Abdullin, S.; Albrow, M.; Anderson, J.; Apollinari, G.; Atac, M.; Bakken, J. A.; Banerjee, S.; Bauerdick, L. A. T.; Beretvas, A.; Berryhill, J.; Bhat, P. C.; Bloch, I.; Borcherding, F.; Burkett, K.; Butler, J. N.; Chetluru, V.; Cheung, H. W. K.; Chlebana, F.; Cihangir, S.; Demarteau, M.; Eartly, D. P.; Elvira, V. D.; Fisk, I.; Freeman, J.; Gao, Y.; Gottschalk, E.; Green, D.; Gunthoti, K.; Gutsche, O.; Hahn, A.; Hanlon, J.; Harris, R. M.; Hirschauer, J.; Hooberman, B.; James, E.; Jensen, H.; Johnson, M.; Joshi, U.; Khatiwada, R.; Kilminster, B.; Klima, B.; Kousouris, K.; Kunori, S.; Kwan, S.; Limon, P.; Lipton, R.; Lykken, J.; Maeshima, K.; Marraffino, J. M.; Mason, D.; McBride, P.; McCauley, T.; Miao, T.; Mishra, K.; Mrenna, S.; Musienko, Y.; Newman-Holmes, C.; O'Dell, V.; Popescu, S.; Pordes, R.; Prokofyev, O.; Saoulidou, N.; Sexton-Kennedy, E.; Sharma, S.; Soha, A.; Spalding, W. J.; Spiegel, L.; Tan, P.; Taylor, L.; Tkaczyk, S.; Uplegger, L.; Vaandering, E. W.; Vidal, R.; Whitmore, J.; Wu, W.; Yang, F.; Yumiceva, F.; Yun, J. C.; Acosta, D.; Avery, P.; Bourilkov, D.; Chen, M.; Di Giovanni, G. P.; Dobur, D.; Drozdetskiy, A.; Field, R. D.; Fisher, M.; Fu, Y.; Furic, I. K.; Gartner, J.; Goldberg, S.; Kim, B.; Klimenko, S.; Konigsberg, J.; Korytov, A.; Kropivnitskaya, A.; Kypreos, T.; Matchev, K.; Mitselmakher, G.; Muniz, L.; Pakhotin, Y.; Prescott, C.; Remington, R.; Schmitt, M.; Scurlock, B.; Sellers, P.; Skhirtladze, N.; Wang, D.; Yelton, J.; Zakaria, M.; Ceron, C.; Gaultney, V.; Kramer, L.; Lebolo, L. M.; Linn, S.; Markowitz, P.; Martinez, G.; Rodriguez, J. L.; Adams, T.; Askew, A.; Bandurin, D.; Bochenek, J.; Chen, J.; Diamond, B.; Gleyzer, S. V.; Haas, J.; Hagopian, S.; Hagopian, V.; Jenkins, M.; Johnson, K. F.; Prosper, H.; Sekmen, S.; Veeraraghavan, V.; Baarmand, M. M.; Dorney, B.; Guragain, S.; Hohlmann, M.; Kaakhety, H.; Ralich, R.; Vodopiyanov, I.; Adams, M. R.; Anghel, I. M.; Apanasevich, L.; Bai, Y.; Bazterra, V. E.; Betts, R. R.; Callner, J.; Cavanaugh, R.; Dragoiu, C.; Garcia-Solis, E. J.; Gerber, C. E.; Hofman, D. J.; Khalatyan, S.; Lacroix, F.; O'Brien, C.; Silvestre, C.; Smoron, A.; Strom, D.; Varelas, N.; Akgun, U.; Albayrak, E. A.; Bilki, B.; Cankocak, K.; Clarida, W.; Duru, F.; Lae, C. K.; McCliment, E.; Merlo, J.-P.; Mermerkaya, H.; Mestvirishvili, A.; Moeller, A.; Nachtman, J.; Newsom, C. R.; Norbeck, E.; Olson, J.; Onel, Y.; Ozok, F.; Sen, S.; Wetzel, J.; Yetkin, T.; Yi, K.; Barnett, B. A.; Blumenfeld, B.; Bonato, A.; Eskew, C.; Fehling, D.; Giurgiu, G.; Gritsan, A. V.; Guo, Z. J.; Hu, G.; Maksimovic, P.; Rappoccio, S.; Swartz, M.; Tran, N. V.; Whitbeck, A.; Baringer, P.; Bean, A.; Benelli, G.; Grachov, O.; Murray, M.; Noonan, D.; Radicci, V.; Sanders, S.; Wood, J. S.; Zhukova, V.; Bolton, T.; Chakaberia, I.; Ivanov, A.; Makouski, M.; Maravin, Y.; Shrestha, S.; Svintradze, I.; Wan, Z.; Gronberg, J.; Lange, D.; Wright, D.; Baden, A.; Boutemeur, M.; Eno, S. C.; Ferencek, D.; Gomez, J. A.; Hadley, N. J.; Kellogg, R. G.; Kirn, M.; Lu, Y.; Mignerey, A. C.; Rossato, K.; Rumerio, P.; Santanastasio, F.; Skuja, A.; Temple, J.; Tonjes, M. B.; Tonwar, S. C.; Twedt, E.; Alver, B.; Bauer, G.; Bendavid, J.; Busza, W.; Butz, E.; Cali, I. A.; Chan, M.; Dutta, V.; Everaerts, P.; Gomez Ceballos, G.; Goncharov, M.; Hahn, K. A.; Harris, P.; Kim, Y.; Klute, M.; Lee, Y.-J.; Li, W.; Loizides, C.; Luckey, P. D.; Ma, T.; Nahn, S.; Paus, C.; Roland, C.; Roland, G.; Rudolph, M.; Stephans, G. S. F.; Sumorok, K.; Sung, K.; Wenger, E. A.; Xie, S.; Yang, M.; Yilmaz, Y.; Yoon, A. S.; Zanetti, M.; Cole, P.; Cooper, S. I.; Cushman, P.; Dahmes, B.; De Benedetti, A.; Dudero, P. R.; Franzoni, G.; Haupt, J.; Klapoetke, K.; Kubota, Y.; Mans, J.; Rekovic, V.; Rusack, R.; Sasseville, M.; Singovsky, A.; Cremaldi, L. M.; Godang, R.; Kroeger, R.; Perera, L.; Rahmat, R.; Sanders, D. A.; Summers, D.; Bloom, K.; Bose, S.; Butt, J.; Claes, D. R.; Dominguez, A.; Eads, M.; Keller, J.; Kelly, T.; Kravchenko, I.; Lazo-Flores, J.; Lundstedt, C.; Malbouisson, H.; Malik, S.; Snow, G. R.; Baur, U.; Godshalk, A.; Iashvili, I.; Kharchilava, A.; Kumar, A.; Smith, K.; Alverson, G.; Barberis, E.; Baumgartel, D.; Boeriu, O.; Chasco, M.; Kaadze, K.; Reucroft, S.; Swain, J.; Wood, D.; Zhang, J.; Anastassov, A.; Kubik, A.; Odell, N.; Ofierzynski, R. A.; Pollack, B.; Pozdnyakov, A.; Schmitt, M.; Stoynev, S.; Velasco, M.; Won, S.; Antonelli, L.; Berry, D.; Hildreth, M.; Jessop, C.; Karmgard, D. J.; Kolb, J.; Kolberg, T.; Lannon, K.; Luo, W.; Lynch, S.; Marinelli, N.; Morse, D. M.; Pearson, T.; Ruchti, R.; Slaunwhite, J.; Valls, N.; Warchol, J.; Wayne, M.; Ziegler, J.; Bylsma, B.; Durkin, L. S.; Gu, J.; Hill, C.; Killewald, P.; Kotov, K.; Ling, T. Y.; Rodenburg, M.; Williams, G.; Adam, N.; Berry, E.; Elmer, P.; Gerbaudo, D.; Halyo, V.; Hebda, P.; Hunt, A.; Jones, J.; Laird, E.; Lopes Pegna, D.; Marlow, D.; Medvedeva, T.; Mooney, M.; Olsen, J.; Piroué, P.; Quan, X.; Saka, H.; Stickland, D.; Tully, C.; Werner, J. S.; Zuranski, A.; Acosta, J. G.; Huang, X. T.; Lopez, A.; Mendez, H.; Oliveros, S.; Ramirez Vargas, J. E.; Zatserklyaniy, A.; Alagoz, E.; Barnes, V. E.; Bolla, G.; Borrello, L.; Bortoletto, D.; Everett, A.; Garfinkel, A. F.; Gecse, Z.; Gutay, L.; Jones, M.; Koybasi, O.; Laasanen, A. T.; Leonardo, N.; Liu, C.; Maroussov, V.; Merkel, P.; Miller, D. H.; Neumeister, N.; Potamianos, K.; Shipsey, I.; Silvers, D.; Svyatkovskiy, A.; Yoo, H. D.; Zablocki, J.; Zheng, Y.; Jindal, P.; Parashar, N.; Boulahouache, C.; Cuplov, V.; Ecklund, K. M.; Geurts, F. J. M.; Liu, J. H.; Morales, J.; Padley, B. P.; Redjimi, R.; Roberts, J.; Zabel, J.; Betchart, B.; Bodek, A.; Chung, Y. S.; de Barbaro, P.; Demina, R.; Eshaq, Y.; Flacher, H.; Garcia-Bellido, A.; Goldenzweig, P.; Gotra, Y.; Han, J.; Harel, A.; Miner, D. C.; Orbaker, D.; Petrillo, G.; Vishnevskiy, D.; Zielinski, M.; Bhatti, A.; Demortier, L.; Goulianos, K.; Lungu, G.; Mesropian, C.; Yan, M.; Atramentov, O.; Barker, A.; Duggan, D.; Gershtein, Y.; Gray, R.; Halkiadakis, E.; Hidas, D.; Hits, D.; Lath, A.; Panwalkar, S.; Patel, R.; Richards, A.; Rose, K.; Schnetzer, S.; Somalwar, S.; Stone, R.; Thomas, S.; Cerizza, G.; Hollingsworth, M.; Spanier, S.; Yang, Z. C.; York, A.; Asaadi, J.; Eusebi, R.; Gilmore, J.; Gurrola, A.; Kamon, T.; Khotilovich, V.; Montalvo, R.; Nguyen, C. N.; Pivarski, J.; Safonov, A.; Sengupta, S.; Tatarinov, A.; Toback, D.; Weinberger, M.; Akchurin, N.; Bardak, C.; Damgov, J.; Jeong, C.; Kovitanggoon, K.; Lee, S. W.; Mane, P.; Roh, Y.; Sill, A.; Volobouev, I.; Wigmans, R.; Yazgan, E.; Appelt, E.; Brownson, E.; Engh, D.; Florez, C.; Gabella, W.; Johns, W.; Kurt, P.; Maguire, C.; Mel, A.; Sheldon, P.; Velkovska, J.; Arenton, M. W.; Balazs, M.; Boutle, S.; Buehler, M.; Conetti, S.; Cox, B.; Francis, B.; Hirosky, R.; Ledovskoy, A.; Lin, C.; Neu, C.; Yohay, R.; Gollapinni, S.; Harr, R.; Karchin, P. E.; Mattson, M.; Milstène, C.; Sakharov, A.; Anderson, M.; Bachtis, M.; Bellinger, J. N.; Carlsmith, D.; Dasu, S.; Efron, J.; Gray, L.; Grogg, K. S.; Grothe, M.; Hall-Wilton, R.; Herndon, M.; Klabbers, P.; Klukas, J.; Lanaro, A.; Lazaridis, C.; Leonard, J.; Lomidze, D.; Loveless, R.; Mohapatra, A.; Parker, W.; Reeder, D.; Ross, I.; Savin, A.; Smith, W. H.; Swanson, J.; Weinberg, M.

2011-01-01

Measurements of inclusive W and Z boson production cross sections in pp collisions at sqrt {s} = 7 TeV are presented, based on 2 .9 pb-1 of data recorded by the CMS detector at the LHC. The measurements, performed in the electron and muon decay channels, are combined to give σ left( {{text{pp}} to {text{W}}X} right) × mathcal{B}left( {{text{W}} to ell ν } right) = 9.95± 0.07left( {{text{stat}}{.}} right)± 0.28left( {{text{syst}}{.}} right)± 1.09 (lumi.) nb and σ left( {{text{pp}} to {text{Z}}X} right) × mathcal{B}left( {Z to {ell+ }{ell- }} right) = 0.931± 0.026left( {{text{stat}}{.}} right)± 0.023left( {{text{syst}}{.}} right)± 0.102 (lumi.) nb, where ℓ stands for either e or μ. Theoretical predictions, calculated at the next-to-next-to-leading order in QCD using recent parton distribution functions, are in agreement with the measured cross sections. Ratios of cross sections, which incur an experimental systematic uncertainty of less than 4%, are also reported.

All roads lead to PP2A: Exploiting the therapeutic potential of this phosphatase

PubMed Central

Sangodkar, Jaya; Farrington, Caroline; McClinch, Kimberly; Galsky, Matthew D.; Kastrinsky, David B.; Narla, Goutham

2015-01-01

Protein phosphatase 2A is a serine/threonine phosphatase involved in the regulation of many cellular processes. A confirmed tumor suppressor protein, PP2A is genetically altered or functionally inactivated in many cancers highlighting a need for its therapeutic reactivation. In this review we will discuss recent literature on PP2A: the elucidation of its structure and the functions of its subunits, and the identification of molecular lesions and post-translational modifications leading to its dysregulation in cancer. A final section will discuss the proteins and small molecules that modulate PP2A and how these might be used to target dysregulated forms of PP2A to treat cancers and other diseases. PMID:26507691

The American Economy in Transition

DTIC Science & Technology

1983-03-01

writes the budget. Business Week pp. 30-2, 11 February 1980. Jameson, Kenneth P. and Joseph Philips . Supply-side economics: a skeptical view. Economic...international monetary policy from World War I1 to the present. Berkeley: Univ. of Calif. Press, 1977. (HG 3881 .B547) Cagan, Philip . Recent monetary...October 1980. 41 Kotler , John. Foreign investments in the United States? Editorial Research Reports pp. 747-64, 12 October 1979. Longenecker, Jane

Release of GTP Exchange Factor Mediated Down-Regulation of Abscisic Acid Signal Transduction through ABA-Induced Rapid Degradation of RopGEFs

PubMed Central

Waadt, Rainer; Schroeder, Julian I.

2016-01-01

The phytohormone abscisic acid (ABA) is critical to plant development and stress responses. Abiotic stress triggers an ABA signal transduction cascade, which is comprised of the core components PYL/RCAR ABA receptors, PP2C-type protein phosphatases, and protein kinases. Small GTPases of the ROP/RAC family act as negative regulators of ABA signal transduction. However, the mechanisms by which ABA controls the behavior of ROP/RACs have remained unclear. Here, we show that an Arabidopsis guanine nucleotide exchange factor protein RopGEF1 is rapidly sequestered to intracellular particles in response to ABA. GFP-RopGEF1 is sequestered via the endosome-prevacuolar compartment pathway and is degraded. RopGEF1 directly interacts with several clade A PP2C protein phosphatases, including ABI1. Interestingly, RopGEF1 undergoes constitutive degradation in pp2c quadruple abi1/abi2/hab1/pp2ca mutant plants, revealing that active PP2C protein phosphatases protect and stabilize RopGEF1 from ABA-mediated degradation. Interestingly, ABA-mediated degradation of RopGEF1 also plays an important role in ABA-mediated inhibition of lateral root growth. The presented findings point to a PP2C-RopGEF-ROP/RAC control loop model that is proposed to aid in shutting off ABA signal transduction, to counteract leaky ABA signal transduction caused by “monomeric” PYL/RCAR ABA receptors in the absence of stress, and facilitate signaling in response to ABA. PMID:27192441

Application of 1,2-diethyl-3-hydroxypyridin-4-one to enhance tissue selectivity for photodynamic therapy of the bladder

NASA Astrophysics Data System (ADS)

Chang, Shi-Chung; MacRobert, Alexander J.; Porter, John B.; Bown, Stephen G.

1995-03-01

Five-aminolaevulinic acid (ALA) induced protoporphyrin IX (PpIX) has proven to be a useful photosensitizer for photodynamic therapy (PDT). In living cells, the conversion of PpIX to photoinactive haem is catalyzed by ferrochelatase in the presence of tissue iron and inhibition of this final committed step results in increased accumulation of PpIX. The in vivo effect of a new iron chelator, 1,2-diethyl-3-hydroxypyridin-4-one (CP94), on the buildup of PpIX in different bladder layers was evaluated. In CP94 treated rats, 5 - 7 hours after intravesical instillation of ALA solution, the fluorescence intensity of PpIX in the urothelium was doubled whilst in the muscle layer it remained low at a similar level to those seen without the iron chelator. With CP94, further reduction of skin photosensitization is possible as a similar photodynamic effect on the bladder could be achieved at lower ALA concentration. The addition of CP94 seems an effective and convenient way to potentiate ALA induced PpIX tissue selectivity.

Synthesis, stability range and characterization of Pr2Cu2O5

NASA Astrophysics Data System (ADS)

Fernández-Sanjulián, Javier; Morán, Emilio; Ángel Alario-Franco, Miguel

2010-03-01

A novel Pr2Cu2O5 phase has been prepared under high-pressure and high-temperature conditions (P ∼6 GPa and T ∼1673 K) in a Belt-type apparatus and characterized by X-ray diffraction and electron microscopy. The crystal structure appears to be an orthorhombic "oxygen-deficient perovskite" (M.T. Anderson, J.T. Vaughey, and K.R. Poeppelmeier, Structural similarities among oxygen-deficient perovskites, Chem. Mater. 5 (1993), pp. 151-165) isostructural with La2Cu2O5 (J.F. Bringley, B.A. Scott, S.J. La Placa, R.F. Boheme, T.M. Shaw, M.W. McElfresh, S.S. Trail, and D.E. Cox, Synthesis of the defect perovskite series LaCuO 3-δ with copper valence varying from 2+to 3+, Nature 347 (1990), pp. 263-265) and Nd2Cu2O5 (B.-H. Chen, D. Walker, E. Suard, B.A. Scott, B. Mercey, M. Hervieu, and B. Raveau, High pressure synthesis of NdCuO3-δ perovskites (0≤δ≤0.5). Inorg. Chem. 34 (1995), pp. 2077-2083).

An extract of Urtica dioica L. mitigates obesity induced insulin resistance in mice skeletal muscle via protein phosphatase 2A (PP2A)

PubMed Central

Obanda, Diana N.; Ribnicky, David; Yu, Yongmei; Stephens, Jacqueline; Cefalu, William T.

2016-01-01

The leaf extract of Urtica dioica L. (UT) has been reported to improve glucose homeostasis in vivo, but definitive studies on efficacy and mechanism of action are lacking. We investigated the effects of UT on obesity- induced insulin resistance in skeletal muscle. Male C57BL/6J mice were divided into three groups: low-fat diet (LFD), high-fat diet (HFD) and HFD supplemented with UT. Body weight, body composition, plasma glucose and plasma insulin were monitored. Skeletal muscle (gastrocnemius) was analyzed for insulin sensitivity, ceramide accumulation and the post translational modification and activity of protein phosphatase 2A (PP2A). PP2A is activated by ceramides and dephosphorylates Akt. C2C12 myotubes exposed to excess free fatty acids with or without UT were also evaluated for insulin signaling and modulation of PP2A. The HFD induced insulin resistance, increased fasting plasma glucose, enhanced ceramide accumulation and PP2A activity in skeletal muscle. Supplementation with UT improved plasma glucose homeostasis and enhanced skeletal muscle insulin sensitivity without affecting body weight and body composition. In myotubes, UT attenuated the ability of FFAs to induce insulin resistance and PP2A hyperactivity without affecting ceramide accumulation and PP2A expression. UT decreased PP2A activity through posttranslational modification that was accompanied by a reduction in Akt dephosphorylation. PMID:26916435

The PP1 binding code: a molecular-lego strategy that governs specificity.

PubMed

Heroes, Ewald; Lesage, Bart; Görnemann, Janina; Beullens, Monique; Van Meervelt, Luc; Bollen, Mathieu

2013-01-01

Ser/Thr protein phosphatase 1 (PP1) is a single-domain hub protein with nearly 200 validated interactors in vertebrates. PP1-interacting proteins (PIPs) are ubiquitously expressed but show an exceptional diversity in brain, testis and white blood cells. The binding of PIPs is mainly mediated by short motifs that dock to surface grooves of PP1. Although PIPs often contain variants of the same PP1 binding motifs, they differ in the number and combination of docking sites. This molecular-lego strategy for binding to PP1 creates holoenzymes with unique properties. The PP1 binding code can be described as specific, universal, degenerate, nonexclusive and dynamic. PIPs control associated PP1 by interference with substrate recruitment or access to the active site. In addition, some PIPs have a subcellular targeting domain that promotes dephosphorylation by increasing the local concentration of PP1. The diversity of the PP1 interactome and the properties of the PP1 binding code account for the exquisite specificity of PP1 in vivo. © 2012 The Authors Journal compilation © 2012 FEBS.

Genomic characteristics of vB_PpaP_PP74, a T7-like Autographivirinae bacteriophage infecting a potato pathogen of the newly proposed species Pectobacterium parmentieri.

PubMed

Kabanova, Anastasia; Shneider, Mikhail; Bugaeva, Eugenia; Ha, Vo Thi Ngoc; Miroshnikov, Kirill; Korzhenkov, Aleksei; Kulikov, Eugene; Toschakov, Stepan; Ignatov, Alexander; Miroshnikov, Konstantin

2018-06-01

Bacteriophage vB_PpaP_PP74 (PP74) is a novel virulent phage that infects members of the species Pectobacterium parmentieri, a newly established species of soft-rot-causing bacteria in the family Pectobacteriaceae, derived from potato-specific Pectobacterium wasabiae. vB_PpaP_PP74 was identified as a member of the family Podoviridae by transmission electron microscopy. The phage has a 39,790-bp dsDNA genome containing 50 open reading frames (ORFs). Because of the absence of genes encoding toxins or lysogeny factors, PP74 may be considered a candidate phage for pathogen biocontrol applications. The genome layout is similar to genomes of T7-like phages within the subfamily Autographivirinae, and therefore, functions can be attributed to most of ORFs. However, the closest nucleotide sequence homologs of phage PP74 are unclassified Escherichia phages. Based on phylogenetic analysis, vB_PpaP_PP74 is a sensu lato T7-like phage, but it forms a distant subgenus group together with homologous enterobacterial phages.

Risk of pneumococcal diseases in adults with underlying medical conditions: a retrospective, cohort study using two Japanese healthcare databases.

PubMed

Imai, Kentaro; Petigara, Tanaz; Kohn, Melvin A; Nakashima, Kei; Aoshima, Masahiro; Shito, Akihito; Kanazu, Shinichi

2018-03-02

To quantify the risk of pneumococcal pneumonia (PP) and invasive pneumococcal disease (IPD) in adults aged ≥19 years with underlying medical conditions compared with healthy adults of the same age in Japan. An observational, retrospective, cohort study using two healthcare claims databases in Japan: Japan Medical Data Center (JMDC) and Medical Data Vision (MDV) databases. A total of 10.4 million individuals, representing 9.3 million person-years of follow-up, were included in the analysis. Eleven medical conditions as well as PP and IPD were identified by the International Statistical Classification of Diseases and Related Health Problems version 10 diagnostic codes and/or local disease codes used in Japan. Adjusted rate ratios (RRs) for PP and IPD in adults with a medical condition versus adults without any medical condition were calculated using multivariate Poisson regression models with age and/or sex as covariates. In the JMDC and MDV databases, respectively, adults ≥19 years with a medical condition (RRs for PP: 3.3 to 13.4, 1.7 to 5.2; RRs for IPD: 12.6 to 43.3, 4.4 to 7.1), adults with two or more medical conditions (PP: 11.6, 2.8; IPD: 18.7, 5.8) and high-risk adults (PP: 12.9, 1.8; IPD: 29.7, 4.0) were at greater risk of PP and IPD compared with their healthy counterparts. Adults aged 50-64 years with an underlying medical condition (PP rate: 38.6 to 212.1 per 100 000 person-years) had a higher rate of PP than those aged ≥65 years without any condition (PP rate: 13.2 to 93.0 per 100 000 person-years). Adults of all ages with an underlying medical condition are at greater risk of PP and IPD compared with adults without any medical condition. This risk increases with the number of underlying medical conditions. Our results support extending pneumococcal vaccination to younger adults with an underlying medical condition, especially those aged 50-64 years. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Parameters Comparsion of Leads Detection in Arctic Sea Ice Using CRYOSAT-2 Waveform Data

NASA Astrophysics Data System (ADS)

Li, J.; Zhang, S.; Xiao, F.; Zhu, C.; Zhang, Y.; Zhu, T.; Yuan, L.

2018-04-01

Leads are only a small part of the polar sea ice structure, but they play a dominant role on the turbulence exchange between the ocean and the atmosphere, they are also important factors about sea ice thickness inversion. Since the early 2000s, Satellite altimetry has been applied to monitor the Arctic sea ice thickness, Satellite altimetry data can be used to distinguish leads and sea ice. In this paper, four parameters including Pulse peakiness (PP), stack standard deviation (SSD), stack kurtosis (SKU) and stack skewness (SSK) are extracted from CryoSat-2 satellite altimetry waveform data. The four parameters are combined into five combinations (PP, PP&SSD, PP&SSD&SKU, PP&SSD&SSK, PP&SSD&SSK&SKU) with constrain conditions to detect the leads. The results of the five methods are compared with MODIS (moderate-resolution imagining spectroradiometer) images and show that, the combination of PP&SSD is better than the single PP, the rest of combinations are the same as the combination of PP&SSD. It turns out, there is no promotion when we add SSK and SKU, successively or simultaneously.

Overlapping functions of bone sialoprotein and pyrophosphate regulators in directing cementogenesis.

PubMed

Ao, M; Chavez, M B; Chu, E Y; Hemstreet, K C; Yin, Y; Yadav, M C; Millán, J L; Fisher, L W; Goldberg, H A; Somerman, M J; Foster, B L

2017-12-01

Although acellular cementum is essential for tooth attachment, factors directing its development and regeneration remain poorly understood. Inorganic pyrophosphate (PP i ), a mineralization inhibitor, is a key regulator of cementum formation: tissue-nonspecific alkaline phosphatase (Alpl/TNAP) null mice (increased PP i ) feature deficient cementum, while progressive ankylosis protein (Ank/ANK) null mice (decreased PP i ) feature increased cementum. Bone sialoprotein (Bsp/BSP) and osteopontin (Spp1/OPN) are multifunctional extracellular matrix components of cementum proposed to have direct and indirect effects on cell activities and mineralization. Studies on dentoalveolar development of Bsp knockout (Bsp -/- ) mice revealed severely reduced acellular cementum, however underlying mechanisms remain unclear. The similarity in defective cementum phenotypes between Bsp -/- mice and Alpl -/- mice (the latter featuring elevated PP i and OPN), prompted us to examine whether BSP is operating by modulating PP i -associated genes. Genetic ablation of Bsp caused a 2-fold increase in circulating PP i , altered mRNA expression of Alpl, Spp1, and Ank, and increased OPN protein in the periodontia. Generation of a Bsp knock-out (KO) cementoblast cell line revealed significantly decreased mineralization capacity, 50% increased PP i in culture media, and increased Spp1 and Ank mRNA expression. While addition of 2μg/ml recombinant BSP altered Spp1, Ank, and Enpp1 expression in cementoblasts, changes resulting from this dose were not dependent on the integrin-binding RGD motif or MAPK/ERK signaling pathway. Decreasing PP i by genetic ablation of Ank on the Bsp -/- mouse background reestablished cementum formation, allowing >3-fold increased acellular cementum volume compared to wild-type (WT). However, deleting Ank did not fully compensate for the absence of BSP. Bsp -/- ; Ank -/- double-deficient mice exhibited mean 20-27% reduced cementum thickness and volume compared to Ank -/- mice. From these data, we conclude that the perturbations in PP i metabolism are not solely driving the cementum pathology in Bsp -/- mice, and that PP i is more potent than BSP as a cementum regulator, as shown by the ability to override loss of BSP by lowering PP i . We propose that BSP and PP i work in concert to direct mineralization in cementum and likely other mineralized tissues. Copyright © 2017 Elsevier Inc. All rights reserved.

Synthesis of Phenanthro[1,10,9,8-cdefg]carbazole-Based Conjugated Polymers for Green-Selective Organic Photodiodes.

PubMed

Sung, Min Jae; Yoon, Seongwon; Kwon, Soon-Ki; Kim, Yun-Hi; Chung, Dae Sung

2016-11-16

A push-pull-type donor copolymer, named PP-TPD, was synthesized with the Suzuki coupling reaction using 6H-phenanthro[1,10,9,8-cdefg]carbazole (PCZ) as the donor unit and 1,3-bis(5-bromothiophen-2-yl)-5-octyl-4H-thieno[3,4-c]pyrrole-4,6(5H)-dione (TPD) as the acceptor unit. The synthesized PP-TPD was systematically investigated in terms of crystallinity and thermal, electrical, electrochemical, and optical properties. PP-TPD revealed green-selective absorption with a narrow full width at half-maximum of 138 nm. Green-selective organic photodiodes (OPDs) were constructed using PP-TPD as the green-absorbing donor and ZnO as the nonabsorbing acceptor material. The fabricated OPDs exhibited an extremely low dark current of 0.68 nA/cm 2 at -5 V and a high detectivity above 10 12 Jones at 550 nm. Moreover, they showed a sufficiently high 3-dB frequency and a linear dynamic range, similar to those of ideal-operating OPDs. The origin and physics background of the observed low dark current and high detectivity are discussed in detail.

Assessing intravascular volume by difference in pulse pressure in pigs submitted to graded hemorrhage.

PubMed

Pestel, Gunther J; Hiltebrand, Luzius B; Fukui, Kimiko; Cohen, Delphine; Hager, Helmut; Kurz, Andrea M

2006-10-01

We assessed changes in intravascular volume monitored by difference in pulse pressure (dPP%) after stepwise hemorrhage in an experimental pig model. Six pigs (23-25 kg) were anesthetized (isoflurane 1.5 vol%) and mechanically ventilated to keep end-tidal CO2 (etCO2) at 35 mmHg. A PA-catheter and an arterial catheter were placed via femoral access. During and after surgery, animals received lactated Ringer's solution as long as they were considered volume responders (dPP>13%). Then animals were allowed to stabilize from the induction of anesthesia and insertion of catheters for 30 min. After stabilization, baseline measurements were taken. Five percent of blood volume was withdrawn, followed by another 5%, and then in 10%-increments until death from exsanguination occurred. After withdrawal of 5% of blood volume, all pigs were considered volume responders (dPP>13%); dPP rose significantly from 6.1+/-3.3% to 19.4+/-4.2%. The regression analysis of stepwise hemorrhage revealed a linear relation between blood loss (hemorrhage in %) and dPP (y=0.99*x+14; R2=0.7764; P<.0001). In addition, dPP was the only parameter that changed significantly between baseline and a blood loss of 5% (P<0.01), whereas cardiac output, stroke volume, heart rate, MAP, central venous pressure, pulmonary artery occlusion pressure, and systemic vascular resistance, respectively, remained unchanged. We conclude that in an experimental hypovolemic pig model, dPP correlates well with blood loss.

Development and assessment of an e-learning course on breast imaging for radiographers: a stratified randomized controlled trial.

PubMed

Moreira, Inês C; Ventura, Sandra Rua; Ramos, Isabel; Rodrigues, Pedro Pereira

2015-01-05

Mammography is considered the best imaging technique for breast cancer screening, and the radiographer plays an important role in its performance. Therefore, continuing education is critical to improving the performance of these professionals and thus providing better health care services. Our goal was to develop an e-learning course on breast imaging for radiographers, assessing its efficacy, effectiveness, and user satisfaction. A stratified randomized controlled trial was performed with radiographers and radiology students who already had mammography training, using pre- and post-knowledge tests, and satisfaction questionnaires. The primary outcome was the improvement in test results (percentage of correct answers), using intention-to-treat and per-protocol analysis. A total of 54 participants were assigned to the intervention (20 students plus 34 radiographers) with 53 controls (19+34). The intervention was completed by 40 participants (11+29), with 4 (2+2) discontinued interventions, and 10 (7+3) lost to follow-up. Differences in the primary outcome were found between intervention and control: 21 versus 4 percentage points (pp), P<.001. Stratified analysis showed effect in radiographers (23 pp vs 4 pp; P=.004) but was unclear in students (18 pp vs 5 pp; P=.098). Nonetheless, differences in students' posttest results were found (88% vs 63%; P=.003), which were absent in pretest (63% vs 63%; P=.106). The per-protocol analysis showed a higher effect (26 pp vs 2 pp; P<.001), both in students (25 pp vs 3 pp; P=.004) and radiographers (27 pp vs 2 pp; P<.001). Overall, 85% were satisfied with the course, and 88% considered it successful. This e-learning course is effective, especially for radiographers, which highlights the need for continuing education.

Development and Assessment of an E-Learning Course on Breast Imaging for Radiographers: A Stratified Randomized Controlled Trial

PubMed Central

Ventura, Sandra Rua; Ramos, Isabel; Rodrigues, Pedro Pereira

2015-01-01

Background Mammography is considered the best imaging technique for breast cancer screening, and the radiographer plays an important role in its performance. Therefore, continuing education is critical to improving the performance of these professionals and thus providing better health care services. Objective Our goal was to develop an e-learning course on breast imaging for radiographers, assessing its efficacy, effectiveness, and user satisfaction. Methods A stratified randomized controlled trial was performed with radiographers and radiology students who already had mammography training, using pre- and post-knowledge tests, and satisfaction questionnaires. The primary outcome was the improvement in test results (percentage of correct answers), using intention-to-treat and per-protocol analysis. Results A total of 54 participants were assigned to the intervention (20 students plus 34 radiographers) with 53 controls (19+34). The intervention was completed by 40 participants (11+29), with 4 (2+2) discontinued interventions, and 10 (7+3) lost to follow-up. Differences in the primary outcome were found between intervention and control: 21 versus 4 percentage points (pp), P<.001. Stratified analysis showed effect in radiographers (23 pp vs 4 pp; P=.004) but was unclear in students (18 pp vs 5 pp; P=.098). Nonetheless, differences in students’ posttest results were found (88% vs 63%; P=.003), which were absent in pretest (63% vs 63%; P=.106). The per-protocol analysis showed a higher effect (26 pp vs 2 pp; P<.001), both in students (25 pp vs 3 pp; P=.004) and radiographers (27 pp vs 2 pp; P<.001). Overall, 85% were satisfied with the course, and 88% considered it successful. Conclusions This e-learning course is effective, especially for radiographers, which highlights the need for continuing education. PMID:25560547

A Cdk9-PP1 switch regulates the elongation-termination transition of RNA polymerase II.

PubMed

Parua, Pabitra K; Booth, Gregory T; Sansó, Miriam; Benjamin, Bradley; Tanny, Jason C; Lis, John T; Fisher, Robert P

2018-06-13

The end of the RNA polymerase II (Pol II) transcription cycle is strictly regulated to prevent interference between neighbouring genes and to safeguard transcriptome integrity 1 . The accumulation of Pol II downstream of the cleavage and polyadenylation signal can facilitate the recruitment of factors involved in mRNA 3'-end formation and termination 2 , but how this sequence is initiated remains unclear. In a chemical-genetic screen, human protein phosphatase 1 (PP1) isoforms were identified as substrates of positive transcription elongation factor b (P-TEFb), also known as the cyclin-dependent kinase 9 (Cdk9)-cyclin T1 (CycT1) complex 3 . Here we show that Cdk9 and PP1 govern phosphorylation of the conserved elongation factor Spt5 in the fission yeast Schizosaccharomyces pombe. Cdk9 phosphorylates both Spt5 and a negative regulatory site on the PP1 isoform Dis2 4 . Sites targeted by Cdk9 in the Spt5 carboxy-terminal domain can be dephosphorylated by Dis2 in vitro, and dis2 mutations retard Spt5 dephosphorylation after inhibition of Cdk9 in vivo. Chromatin immunoprecipitation and sequencing analysis indicates that Spt5 is dephosphorylated as transcription complexes traverse the cleavage and polyadenylation signal, concomitant with the accumulation of Pol II phosphorylated at residue Ser2 of the carboxy-terminal domain consensus heptad repeat 5 . A conditionally lethal Dis2-inactivating mutation attenuates the drop in Spt5 phosphorylation on chromatin, promotes transcription beyond the normal termination zone (as detected by precision run-on transcription and sequencing 6 ) and is genetically suppressed by the ablation of Cdk9 target sites in Spt5. These results suggest that the transition of Pol II from elongation to termination coincides with a Dis2-dependent reversal of Cdk9 signalling-a switch that is analogous to a Cdk1-PP1 circuit that controls mitotic progression 4 .

Methylation-regulated decommissioning of multimeric PP2A complexes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Cheng-Guo; Zheng, Aiping; Jiang, Li

2017-12-01

Dynamic assembly/disassembly of signaling complexes are crucial for cellular functions. Specialized latency and activation chaperones control the biogenesis of protein phosphatase 2A (PP2A) holoenzymes that contain a common scaffold and catalytic subunits and a variable regulatory subunit. Here we show that the butterfly-shaped TIPRL (TOR signaling pathway regulator) makes highly integrative multibranching contacts with the PP2A catalytic subunit, selective for the unmethylated tail and perturbing/inactivating the phosphatase active site. TIPRL also makes unusual wobble contacts with the scaffold subunit, allowing TIPRL, but not the overlapping regulatory subunits, to tolerate disease-associated PP2A mutations, resulting in reduced holoenzyme assembly and enhanced inactivationmore » of mutant PP2A. Strikingly, TIPRL and the latency chaperone, α4, coordinate to disassemble active holoenzymes into latent PP2A, strictly controlled by methylation. Our study reveals a mechanism for methylation-responsive inactivation and holoenzyme disassembly, illustrating the complexity of regulation/signaling, dynamic complex disassembly, and disease mutations in cancer and intellectual disability.« less

Sodium pyrophosphate enhances iron bioavailability from bouillon cubes fortified with ferric pyrophosphate.

PubMed

Cercamondi, Colin I; Duchateau, Guus S M J E; Harika, Rajwinder K; van den Berg, Robin; Murray, Peter; Koppenol, Wieneke P; Zeder, Christophe; Zimmermann, Michael B; Moretti, Diego

2016-08-01

Fe fortification of centrally manufactured and frequently consumed condiments such as bouillon cubes could help prevent Fe deficiency in developing countries. However, Fe compounds that do not cause sensory changes in the fortified product, such as ferric pyrophosphate (FePP), exhibit low absorption in humans. Tetra sodium pyrophosphate (NaPP) can form soluble complexes with Fe, which could increase Fe bioavailability. Therefore, the aim of this study was to investigate Fe bioavailability from bouillon cubes fortified with either FePP only, FePP+NaPP, ferrous sulphate (FeSO4) only, or FeSO4+NaPP. We first conducted in vitro studies using a protocol of simulated digestion to assess the dialysable and ionic Fe, and the cellular ferritin response in a Caco-2 cell model. Second, Fe absorption from bouillon prepared from intrinsically labelled cubes (2·5 mg stable Fe isotopes/cube) was assessed in twenty-four Fe-deficient women, by measuring Fe incorporation into erythrocytes 2 weeks after consumption. Fe bioavailability in humans increased by 46 % (P<0·005) when comparing bouillons fortified with FePP only (4·4 %) and bouillons fortified with FePP+NaPP (6·4 %). Fe absorption from bouillons fortified with FeSO4 only and with FeSO4+NaPP was 33·8 and 27·8 %, respectively (NS). The outcome from the human study is in agreement with the dialysable Fe from the in vitro experiments. Our findings suggest that the addition of NaPP could be a promising strategy to increase Fe absorption from FePP-fortified bouillon cubes, and if confirmed by further research, for other fortified foods with complex food matrices as well.

SAV1 promotes Hippo kinase activation through antagonizing the PP2A phosphatase STRIPAK

PubMed Central

Osinski, Adam; Tomchick, Diana R; Brautigam, Chad A

2017-01-01

The Hippo pathway controls tissue growth and homeostasis through a central MST-LATS kinase cascade. The scaffold protein SAV1 promotes the activation of this kinase cascade, but the molecular mechanisms remain unknown. Here, we discover SAV1-mediated inhibition of the PP2A complex STRIPAKSLMAP as a key mechanism of MST1/2 activation. SLMAP binding to autophosphorylated MST2 linker recruits STRIPAK and promotes PP2A-mediated dephosphorylation of MST2 at the activation loop. Our structural and biochemical studies reveal that SAV1 and MST2 heterodimerize through their SARAH domains. Two SAV1–MST2 heterodimers further dimerize through SAV1 WW domains to form a heterotetramer, in which MST2 undergoes trans-autophosphorylation. SAV1 directly binds to STRIPAK and inhibits its phosphatase activity, protecting MST2 activation-loop phosphorylation. Genetic ablation of SLMAP in human cells leads to spontaneous activation of the Hippo pathway and alleviates the need for SAV1 in Hippo signaling. Thus, SAV1 promotes Hippo activation through counteracting the STRIPAKSLMAP PP2A phosphatase complex. PMID:29063833

SAV1 promotes Hippo kinase activation through antagonizing the PP2A phosphatase STRIPAK

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bae, Sung Jun; Ni, Lisheng; Osinski, Adam

The Hippo pathway controls tissue growth and homeostasis through a central MST-LATS kinase cascade. The scaffold protein SAV1 promotes the activation of this kinase cascade, but the molecular mechanisms remain unknown. Here, we discover SAV1-mediated inhibition of the PP2A complex STRIPAKSLMAP as a key mechanism of MST1/2 activation. SLMAP binding to autophosphorylated MST2 linker recruits STRIPAK and promotes PP2A-mediated dephosphorylation of MST2 at the activation loop. Our structural and biochemical studies reveal that SAV1 and MST2 heterodimerize through their SARAH domains. Two SAV1–MST2 heterodimers further dimerize through SAV1 WW domains to form a heterotetramer, in which MST2 undergoes trans-autophosphorylation. SAV1more » directly binds to STRIPAK and inhibits its phosphatase activity, protecting MST2 activation-loop phosphorylation. Genetic ablation of SLMAP in human cells leads to spontaneous activation of the Hippo pathway and alleviates the need for SAV1 in Hippo signaling. Thus, SAV1 promotes Hippo activation through counteracting the STRIPAKSLMAP PP2A phosphatase complex.« less

Development of temperature-based algorithms for the estimation of microphytobenthic primary production in a tidal flat: A case study in Daebu mudflat, Korea.

PubMed

Kwon, Bong-Oh; Kim, Hae-Cheol; Koh, Chul-Hwan; Ryu, Jongseong; Son, SeungHyun; Kim, Yong Hoon; Khim, Jong Seong

2018-05-23

This study presents the results of field experiments that were designed to investigate the photophysiological characteristics of microphytobenthos (MPB) and to estimate primary production (PP) in Daebu mudflat, which is located at the west coast of Korea. A typical seasonal (or monthly) fluctuation of intertidal MPB PP was found in association with biotic (benthic Chl-a) and/or abiotic parameters (irradiance and temperature) over a period of three years. From a series of field-laboratory experiments using the oxygen micro-profiling method (totaling 28 surveys), three consistent phenomena were observed: 1) winter to early spring algal blooms, 2) seasonal changes in Q 10 , and 3) temperature dependent MPB photosynthesis-irradiance (P-I). In particular, both the chlorophyll-specific maximum photosynthetic capacity (P b max ) and the saturated light intensity (I k ), derived from 126 P-I curves (1870 data sets of oxygen micro-profiling in the sediment), were significantly correlated with sediment temperature (p < 0.01). To develop an empirical MPB PP model, the relationships between P-I parameters and environmental variables were parameterized following established exponential forms (e.g., Q 10 ). It was possible to estimate the MPB PP in Daebu mudflat area by using easily accessible explanatory factor, suitable to be used for future explorations of parameters such as sediment temperature, irradiance, chlorophyll concentration, and tidal height. The estimated annual MPB PP based on the empirical PP model were found to be greater than that in the Wadden Sea and average annual PP in the temperate zones of the world. Authors believe that the present approach of the MPB PP estimation could be combined with remote-sensing techniques (e.g., satellites) to support coastal ecosystem management. Copyright © 2018 Elsevier Ltd. All rights reserved.

Design of a novel theranostic nanomedicine: synthesis and physicochemical properties of a biocompatible polyphosphazene-platinum(II) conjugate.

PubMed

Avaji, Prakash G; Park, Jung Hyun; Lee, Hyun Jeong; Jun, Yong Joo; Park, Kyung Su; Lee, Kyung Eun; Choi, Soo-Jin; Lee, Hwa Jeong; Sohn, Youn Soo

2016-01-01

To develop a theranostic nanomedicine involving the antitumor-active moiety (dach)Pt(II) (dach: trans-(±)-1,2-diaminocyclohexane) of oxaliplatin (OX), a new biocompatible polyphosphazene carrier polymer was designed by grafting with a methoxy poly(ethylene glycol) (MPEG) to increase duration of circulation in the blood and with aminoethanol (AE) as a spacer group. The antitumor (dach)Pt moiety was conjugated to the carrier polymer using cis-aconitic acid (AA) as a linker, resulting in a polymer conjugate formulated as [NP(MPEG550)(AE-AA)Pt(dach)]n, named "Polyplatin" (PP). PP was found to self-assemble into very stable polymeric nanoparticles with a mean diameter of 55.1 nm and a critical aggregation concentration of 18.5 mg/L in saline. PP could easily be labeled with a fluorescence dye such as Cy5.5 for imaging studies. The time-dependent ex vivo image studies on organ distributions and clearance of Cy-labeled PP have shown that PP accumulated in the tumor with high selectivity by the enhanced permeability and retention effect but was cleared out from all the major organs including the liver in about 4 weeks postinjection. Another time-dependent bioimaging study on distribution and clearance of PP in mouse kidney using laser ablation inductively coupled plasma mass spectroscopy has shown that PP accumulates much less in kidney and is more rapidly excreted than monomeric OX, which is in accord with the very low acute toxicity of PP as shown by its high LD50 value of more than 2000 mg/kg. The pharmacokinetic study of PP has shown that it has a much longer half-life (t 1/2β) of 13.3 hours compared with the 5.21 hours of OX and about a 20 times higher area under the curve value of 42,850.8 ng h/mL compared with the 2,320.4 ng h/mL of OX. The nude mouse xenograft trials of PP against the gastric MKN-28 tumor cell line exhibited remarkably better tumor efficacy compared with OX at the higher tolerated dose, with lower systemic toxicity.

Cytokines Alter Glucocorticoid Receptor Phosphorylation in Airway Cells

PubMed Central

Bouazza, Belaid; Krytska, Kateryna; Debba-Pavard, Manel; Amrani, Yassine; Honkanen, Richard E.; Tran, Jennifer

2012-01-01

Corticosteroid insensitivity (CSI) represents a profound challenge in managing patients with asthma. We recently demonstrated that short exposure of airway smooth muscle cells (ASMCs) to proasthmatic cytokines drastically reduced their responsiveness to glucocorticoids (GCs), an effect that was partially mediated via interferon regulatory factor-1, suggesting the involvement of additional mechanisms (Am J Respir Cell Mol Biol 2008;38:463–472). Although GC receptor (GR) can be phosphorylated at multiple serines in the N-terminal region, the major phosphorylation sites critical for GR transcriptional activity are serines 211 (Ser211) and 226 (Ser226). We tested the novel hypothesis that cytokine-induced CSI in ASMCs is due to an impaired GR phosphorylation. Cells were treated with TNF-α (10 ng/ml) and IFN-γ (500 UI/ml) for 6 hours and/or fluticasone (100 nm) added 2 hours before. GR was constitutively phosphorylated at Ser226 but not at Ser211 residues. Cytokines dramatically suppressed fluticasone-induced phosphorylation of GR on Ser211 but not on Ser226 residues while increasing the expression of Ser/Thr protein phosphatase (PP)5 but not that of PP1 or PP2A. Transfection studies using a reporter construct containing GC responsive elements showed that the specific small interfering RNA–induced mRNA knockdown of PP5, but not that of PP1 or PP2A, partially prevented the cytokine suppressive effects on GR-meditated transactivation activity. Similarly, cytokines failed to inhibit GC-induced GR-Ser211 phosphorylation when expression of PP5 was suppressed. We propose that the novel mechanism that proasthmatic cytokine-induced CSI in ASMCs is due, in part, to PP5-mediated impairment of GR-Ser211 phosphorylation. PMID:22592921

Molecular cloning, expression and single nucleotide polymorphisms of protein phosphatase 1 (PP1) in mandarin fish (Siniperca chuatsi).

PubMed

Cheng, Xiao-Yan; He, Shan; Liang, Xu-Fang; Song, Yi; Yuan, Xiao-Chen; Li, Ling; Wen, Zheng-Yong; Cai, Wen-Jing; Tao, Ya-Xiong

2015-11-01

In the wild, mandarin fish (Siniperca chuatsi) only feed on live prey fish, refusing dead prey. When reared in ponds, training will result in some mandarin fish accepting artificial diets. However, little is currently known about the molecular mechanism of the individual difference. Serine/threonine protein phosphatase 1 (PP1) is a suppressor of learning and long-term memory (LTM) in mammals. In the present study, the relationship between PP1 and the individual difference in acceptance of artificial diets in mandarin fish was investigated. The complete CDS (coding sequence) of four PP1 isoforms (PP1caa, PP1cab, PP1cb and PP1cc) were cloned in mandarin fish. The amino acid sequences of these PP1 isoforms are highly conserved in different species. The mRNA expressions of PP1caa and PP1cb in brain of artificial diet feeders were significantly higher than those in nonfeeders, suggesting the deficiency in the maintenance of long-term memory of its natural food habit (live prey fish). The SNP loci in PP1caa and PP1cb were also found to be associated with the individual difference in acceptance of artificial diets in mandarin fish. These SNPs of PP1caa and PP1cb genes could be useful markers for gene-associated breeding of mandarin fish, which could accept artificial diets. In conclusion, different mRNA expression and SNPs of PP1caa and PP1cb genes in feeders and nonfeeders of artificial diets might contribute to understanding the molecular mechanism of individual difference in acceptance of artificial diets in mandarin fish. Copyright © 2015 Elsevier Inc. All rights reserved.

Association of PAEs with Precocious Puberty in Children: A Systematic Review and Meta-Analysis.

PubMed

Wen, Yi; Liu, Shu-Dan; Lei, Xun; Ling, Yu-Shuang; Luo, Yan; Liu, Qin

2015-12-01

Precocious puberty (PP) currently affects 1 in 5000 children and is 10 times more common in girls. Existing studies have tried to detect an association between phathalic acid esters (PAEs) and PP, but the results did not reach a consensus. To estimate the association between PAEs and children with PP based on current evidence. Databases including PubMed (1978 to March 2015), OVID (1946 to March 2015), Web of Science (1970 to March 2015), EBSCO (1976 to March 2015), CNKI (1979 to March 2015), WANFANG DATA (1987 to March 2015), CBM (1978 to March 2015) and CQVIP (1989 to March 2015) were searched to identify all case-control studies that determined the exposure and concentration of PAEs and their metabolites in children with PP. Meta-analysis of the pooled standard mean difference (SMD) and odds ratio (OR) with 95% confidence intervals (CI) were calculated. A total of 14 studies involving 2223 subjects were finally included. The pooled estimates showed that PP was associated with di-(2-ethylhexyl)-phthalate (DEHP) exposure (OR: 3.90, 95% CI: 2.77 to 5.49). Besides, the concentration of DEHP (SMD: 1.73, 95% CI: 0.54 to 2.91) and di-n-butyl phthalate (DBP) (SMD: 4.31, 95% CI: 2.67 to 5.95) in the PP group were significantly higher than those in the control group, respectively, while no difference was detected between case and control groups in either serum or urinary concentration of mono-(2-ethylhexyl)-phthalate (MEHP), monobutyl phthalate (MBP), mono(2-ethyl-5-oxohexyl) phthalate(MEOHP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), monomethyl phthalate (MMP), monobenzyl phthalate (MBzP) or monoethyl phthalate (MEP). Exposure of DEHP and DBP might be associated with PP risk for girls, however, there is no evidence to show an association between the exposure to most PAE metabolites and PP. Given the moderate strength of the results, well-designed cohort studies with large sample size should be performed in future.

The RDF and Amphibious Warfare.

DTIC Science & Technology

1982-03-01

Retrieval oy Manfred Kocnen," 10 pp., Mcr 78 lPuolisnea 3s a Letter to the Editor, Journal of Documentation, vol. 31 , PP 226 No. 4, pages 298-301...ctlon rants,w 25 pp., 3cr 1979, ’C 4061 529 𔃿 ’~~~~~~-s’. Roa~ ., n a .e~nn mlzrani, marce i~., "The 38,i:,asslcaI -- efs70 71 . Soverai 5xiIeCTlI...a Vtaas," 71 Do-. an 1981, A2 V96.)5q 0nln 1. OIme0 2 -P 300 pp 313 Jondow. James and Schmildt. Peter, * wOn tha Estimation of Roberts, Stephen S

Protein Phosphatase 2A Antagonizes ATM and ATR in a Cdk2- and Cdc7-Independent DNA Damage Checkpoint

PubMed Central

Petersen, Paris; Chou, Danny M.; You, Zhongsheng; Hunter, Tony; Walter, Johannes C.; Walter, Gernot

2006-01-01

We previously used a soluble cell-free system derived from Xenopus eggs to investigate the role of protein phosphatase 2A (PP2A) in chromosomal DNA replication. We found that immunodepletion of PP2A or inhibition of PP2A by okadaic acid (OA) inhibits initiation of DNA replication by preventing loading of the initiation factor Cdc45 onto prereplication complexes. Evidence was provided that PP2A counteracts an inhibitory protein kinase that phosphorylates and inactivates a crucial Cdc45 loading factor. Here, we report that the inhibitory effect of OA is abolished by caffeine, an inhibitor of the checkpoint kinases ataxia-telangiectasia mutated protein (ATM) and ataxia-telangiectasia related protein (ATR) but not by depletion of ATM or ATR from the extract. Furthermore, we demonstrate that double-strand DNA breaks (DSBs) cause inhibition of Cdc45 loading and initiation of DNA replication and that caffeine, as well as immunodepletion of either ATM or ATR, abolishes this inhibition. Importantly, the DSB-induced inhibition of Cdc45 loading is prevented by addition of the catalytic subunit of PP2A to the extract. These data suggest that DSBs and OA prevent Cdc45 loading through different pathways, both of which involve PP2A, but only the DSB-induced checkpoint implicates ATM and ATR. The inhibitory effect of DSBs on Cdc45 loading does not result from downregulation of cyclin-dependent kinase 2 (Cdk2) or Cdc7 activity and is independent of Chk2. However, it is partially dependent on Chk1, which becomes phosphorylated in response to DSBs. These data suggest that PP2A counteracts ATM and ATR in a DNA damage checkpoint in Xenopus egg extracts. PMID:16479016

Cysteine-grafted nonwoven geotextile: a new and efficient material for heavy metals sorption--Part B.

PubMed

Vandenbossche, M; Vezin, H; Touati, N; Jimenez, M; Casetta, M; Traisnel, M

2014-10-01

The development of a new material designed to trap heavy metals from sediments or wastewater, based on a polypropylene non-woven covalently grafted with cysteine, has been reported in a previous paper (Part A). The non-woven was first functionalized with acrylic acid (AA) which is used as spacer, and then cysteine was immobilized on the substrate through covalent coupling in order to obtain the so-called PP-g-AA-cysteine. Some preliminary heavy metals adsorption tests gave interesting results: at 20 °C for 24 h and in a 1000 mg/L heavy metals solution, PP-g-AA-cysteine adsorbs 95 mg Cu/g PP (CuSO4 solution), 104 mg Cu/g PP (Cu(NO3)2 solution), 135 mg Pb/g PP (Pb(NO3)2 solution) and 21 mg Cr/g PP (Cr(NO3)3 solution). In this second part of the work, heavy metals sorption tests were carried out with Cu (II), Pb (II), and Cr (III) separately, in order to determine the sorption capacity of this new sorbent as a function of (i) the heavy metals concentration in the solution, (ii) the contact time with the solution, (iii) the pH and (iv) the ionic strength of the solution containing heavy metals. Moreover, the sorption capacity of PP-g-AA-Cysteine was studied using a polluted solution consisting of a mixture of these different heavy metals. An Electron Paramagnetic Resonance study was finally carried out in order to determine the coordination geometry in the environment of the copper trapped by the PP-g-AA-cysteine. Copyright © 2014 Elsevier Ltd. All rights reserved.

Measurement of the total cross section from elastic scattering in pp collisions at √s=7 TeV with the ATLAS detector

DOE PAGES

Aad, G.; Abbott, B.; Abdallah, J.; ...

2014-10-28

In this study, a measurement of the totalmore » $pp$ cross section at the LHC at $$\\sqrt{s}=7$$ TeV is presented. In a special run with high-$$\\beta^{\\star}$$ beam optics, an integrated luminosity of 80 µb -1 was accumulated in order to measure the differential elastic cross section as a function of the Mandelstam momentum transfer variable $t$. The measurement is performed with the ALFA sub-detector of ATLAS. Using a fit to the differential elastic cross section in the |t| range from 0.01 GeV 2 to 0.1 GeV 2 to extrapolate to |t| → 0, the total cross section, σ tot($pp$ → X), is measured via the optical theorem to be: σ tot($pp$ → X) = 95.35 ± 0.38 (stat.) ± 1.25 (exp.) ± 0.37 (extr.) mb, where the first error is statistical, the second accounts for all experimental systematic uncertainties and the last is related to uncertainties in the extrapolation to |t| → 0. In addition, the slope of the elastic cross section at small |t| is determined to be B = 19.73 ± 0.14 (stat.) ± 0.26 (syst.) GeV -2.« less

Measurement of the total cross section from elastic scattering in pp collisions at √s=7 TeV with the ATLAS detector

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aad, G.; Abbott, B.; Abdallah, J.

In this study, a measurement of the totalmore » $pp$ cross section at the LHC at $$\\sqrt{s}=7$$ TeV is presented. In a special run with high-$$\\beta^{\\star}$$ beam optics, an integrated luminosity of 80 µb -1 was accumulated in order to measure the differential elastic cross section as a function of the Mandelstam momentum transfer variable $t$. The measurement is performed with the ALFA sub-detector of ATLAS. Using a fit to the differential elastic cross section in the |t| range from 0.01 GeV 2 to 0.1 GeV 2 to extrapolate to |t| → 0, the total cross section, σ tot($pp$ → X), is measured via the optical theorem to be: σ tot($pp$ → X) = 95.35 ± 0.38 (stat.) ± 1.25 (exp.) ± 0.37 (extr.) mb, where the first error is statistical, the second accounts for all experimental systematic uncertainties and the last is related to uncertainties in the extrapolation to |t| → 0. In addition, the slope of the elastic cross section at small |t| is determined to be B = 19.73 ± 0.14 (stat.) ± 0.26 (syst.) GeV -2.« less

Leptoquark toolbox for precision collider studies

NASA Astrophysics Data System (ADS)

Doršner, Ilja; Greljo, Admir

2018-05-01

We implement scalar and vector leptoquark (LQ) models in the universal FeynRules output (UFO) format assuming the Standard Model fermion content and conservation of baryon and lepton numbers. Scalar LQ implementations include next-to-leading order (NLO) QCD corrections. We report the NLO QCD inclusive cross sections in proton-proton collisions at 13 TeV, 14 TeV, and 27 TeV for all on-shell LQ production processes. These comprise (i) LQ pair production ( pp → ΦΦ) and (ii) single LQ + lepton production ( pp → Φ ℓ) for all initial quark flavours ( u, d, s, c, and b). Vector LQ implementation includes adjustable non-minimal QCD coupling. We discuss several aspects of LQ searches at a hadron collider, emphasising the implications of SU(2) gauge invariance, electroweak and flavour constraints, on the possible signatures. Finally, we outline the high- p T search strategy for LQs recently proposed in the literature to resolve experimental anomalies in B-meson decays. In this context, we stress the importance of complementarity of the three LQ related processes, namely, pp → ΦΦ, pp → Φ ℓ, and pp → ℓℓ.

Measurement of the Lambda b0 lifetime in Lambda b0-->J/psi Lambda 0 in pp collisions at square root s=1.96 TeV.

PubMed

Abulencia, A; Adelman, J; Affolder, T; Akimoto, T; Albrow, M G; Ambrose, D; Amerio, S; Amidei, D; Anastassov, A; Anikeev, K; Annovi, A; Antos, J; Aoki, M; Apollinari, G; Arguin, J-F; Arisawa, T; Artikov, A; Ashmanskas, W; Attal, A; Azfar, F; Azzi-Bacchetta, P; Azzurri, P; Bacchetta, N; Badgett, W; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Baroiant, S; Bartsch, V; Bauer, G; Bedeschi, F; Behari, S; Belforte, S; Bellettini, G; Bellinger, J; Belloni, A; Benjamin, D; Beretvas, A; Beringer, J; Berry, T; Bhatti, A; Binkley, M; Bisello, D; Blair, R E; Blocker, C; Blumenfeld, B; Bocci, A; Bodek, A; Boisvert, V; Bolla, G; Bolshov, A; Bortoletto, D; Boudreau, J; Boveia, A; Brau, B; Brigliadori, L; Bromberg, C; Brubaker, E; Budagov, J; Budd, H S; Budd, S; Budroni, S; Burkett, K; Busetto, G; Bussey, P; Byrum, K L; Cabrera, S; Campanelli, M; Campbell, M; Canelli, F; Canepa, A; Carrillo, S; Carlsmith, D; Carosi, R; Carron, S; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chang, S H; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, I; Cho, K; Chokheli, D; Chou, J P; Choudalakis, G; Chuang, S H; Chung, K; Chung, W H; Chung, Y S; Ciljak, M; Ciobanu, C I; Ciocci, M A; Clark, A; Clark, D; Coca, M; Compostella, G; Convery, M E; Conway, J; Cooper, B; Copic, K; Cordelli, M; Cortiana, G; Crescioli, F; Cuenca Almenar, C; Cuevas, J; Culbertson, R; Cully, J C; Cyr, D; DaRonco, S; D'Auria, S; Davies, T; D'Onofrio, M; Dagenhart, D; de Barbaro, P; De Cecco, S; Deisher, A; De Lentdecker, G; Dell'Orso, M; Delli Paoli, F; Demortier, L; Deng, J; Deninno, M; De Pedis, D; Derwent, P F; Di Giovanni, G P; Dionisi, C; Di Ruzza, B; Dittmann, J R; DiTuro, P; Dörr, C; Donati, S; Donega, M; Dong, P; Donini, J; Dorigo, T; Dube, S; Efron, J; Erbacher, R; Errede, D; Errede, S; Eusebi, R; Fang, H C; Farrington, S; Fedorko, I; Fedorko, W T; Feild, R G; Feindt, M; Fernandez, J P; Field, R; Flanagan, G; Foland, A; Forrester, S; Foster, G W; Franklin, M; Freeman, J C; Furic, I; Gallinaro, M; Galyardt, J; Garcia, J E; Garberson, F; Garfinkel, A F; Gay, C; Gerberich, H; Gerdes, D; Giagu, S; Giannetti, P; Gibson, A; Gibson, K; Gimmell, J L; Ginsburg, C; Giokaris, N; Giordani, M; Giromini, P; Giunta, M; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldschmidt, N; Goldstein, J; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gresele, A; Griffiths, M; Grinstein, S; Grosso-Pilcher, C; Group, R C; Grundler, U; Guimaraes da Costa, J; Gunay-Unalan, Z; Haber, C; Hahn, K; Hahn, S R; Halkiadakis, E; Hamilton, A; Han, B-Y; Han, J Y; Handler, R; Happacher, F; Hara, K; Hare, M; Harper, S; Harr, R F; Harris, R M; Hartz, M; Hatakeyama, K; Hauser, J; Heijboer, A; Heinemann, B; Heinrich, J; Henderson, C; Herndon, M; Heuser, J; Hidas, D; Hill, C S; Hirschbuehl, D; Hocker, A; Holloway, A; Hou, S; Houlden, M; Hsu, S-C; Huffman, B T; Hughes, R E; Husemann, U; Huston, J; Incandela, J; Introzzi, G; Iori, M; Ishizawa, Y; Ivanov, A; Iyutin, B; James, E; Jang, D; Jayatilaka, B; Jeans, D; Jensen, H; Jeon, E J; Jindariani, S; Jones, M; Joo, K K; Jun, S Y; Jung, J E; Junk, T R; Kamon, T; Karchin, P E; Kato, Y; Kemp, Y; Kephart, R; Kerzel, U; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kimura, N; Kirsch, L; Klimenko, S; Klute, M; Knuteson, B; Ko, B R; Kondo, K; Kong, D J; Konigsberg, J; Korytov, A; Kotwal, A V; Kovalev, A; Kraan, A C; Kraus, J; Kravchenko, I; Kreps, M; Kroll, J; Krumnack, N; Kruse, M; Krutelyov, V; Kubo, T; Kuhlmann, S E; Kuhr, T; Kusakabe, Y; Kwang, S; Laasanen, A T; Labarga, L; Lai, S; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; Lazzizzera, I; LeCompte, T; Lee, J; Lee, J; Lee, Y J; Lee, S W; Lefèvre, R; Leonardo, N; Leone, S; Levy, S; Lewis, J D; Lin, C; Lin, C S; Lindgren, M; Lipeles, E; Liss, T M; Lister, A; Litvintsev, D O; Liu, T; Lockyer, N S; Loginov, A; Loreti, M; Loverre, P; Lu, R-S; Lucchesi, D; Lujan, P; Lukens, P; Lungu, G; Lyons, L; Lys, J; Lysak, R; Lytken, E; Mack, P; MacQueen, D; Madrak, R; Maeshima, K; Makhoul, K; Maki, T; Maksimovic, P; Malde, S; Manca, G; Margaroli, F; Marginean, R; Marino, C; Marino, C P; Martin, A; Martin, M; Martin, V; Martínez, M; Maruyama, T; Mastrandrea, P; Masubuchi, T; Matsunaga, H; Mattson, M E; Mazini, R; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Menzemer, S; Menzione, A; Merkel, P; Mesropian, C; Messina, A; Miao, T; Miladinovic, N; Miles, J; Miller, R; Mills, C; Milnik, M; Mitra, A; Mitselmakher, G; Miyamoto, A; Moed, S; Moggi, N; Mohr, B; Moore, R; Morello, M; Movilla Fernandez, P; Mülmenstädt, J; Mukherjee, A; Muller, Th; Mumford, R; Murat, P; Nachtman, J; Nagano, A; Naganoma, J; Nahn, S; Nakano, I; Napier, A; Necula, V; Neu, C; Neubauer, M S; Nielsen, J; Nigmanov, T; Nodulman, L; Norniella, O; Nurse, E; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Oldeman, R; Orava, R; Osterberg, K; Pagliarone, C; Palencia, E; Papadimitriou, V; Paramonov, A A; Parks, B; Pashapour, S; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Piedra, J; Pinera, L; Pitts, K; Plager, C; Pondrom, L; Portell, X; Poukhov, O; Pounder, N; Prokoshin, F; Pronko, A; Proudfoot, J; Ptochos, F; Punzi, G; Pursley, J; Rademacker, J; Rahaman, A; Ranjan, N; Rappoccio, S; Reisert, B; Rekovic, V; Renton, P; Rescigno, M; Richter, S; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rogers, E; Rolli, S; Roser, R; Rossi, M; Rossin, R; Ruiz, A; Russ, J; Rusu, V; Saarikko, H; Sabik, S; Safonov, A; Sakumoto, W K; Salamanna, G; Saltó, O; Saltzberg, D; Sánchez, C; Santi, L; Sarkar, S; Sartori, L; Sato, K; Savard, P; Savoy-Navarro, A; Scheidle, T; Schlabach, P; Schmidt, E E; Schmidt, M P; Schmitt, M; Schwarz, T; Scodellaro, L; Scott, A L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semenov, A; Sexton-Kennedy, L; Sfyrla, A; Shapiro, M D; Shears, T; Shepard, P F; Sherman, D; Shimojima, M; Shochet, M; Shon, Y; Shreyber, I; Sidoti, A; Sinervo, P; Sisakyan, A; Sjolin, J; Slaughter, A J; Slaunwhite, J; Sliwa, K; Smith, J R; Snider, F D; Snihur, R; Soderberg, M; Soha, A; Somalwar, S; Sorin, V; Spalding, J; Spinella, F; Spreitzer, T; Squillacioti, P; Stanitzki, M; Staveris-Polykalas, A; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Stuart, D; Suh, J S; Sukhanov, A; Sun, H; Suzuki, T; Taffard, A; Takashima, R; Takeuchi, Y; Takikawa, K; Tanaka, M; Tanaka, R; Tecchio, M; Teng, P K; Terashi, K; Tesarek, R J; Thom, J; Thompson, A S; Thomson, E; Tipton, P; Tiwari, V; Tkaczyk, S; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Tourneur, S; Trischuk, W; Tsuchiya, R; Tsuno, S; Turini, N; Ukegawa, F; Unverhau, T; Uozumi, S; Usynin, D; Vallecorsa, S; van Remortel, N; Varganov, A; Vataga, E; Vázquez, F; Velev, G; Veramendi, G; Veszpremi, V; Vidal, R; Vila, I; Vilar, R; Vine, T; Vollrath, I; Volobouev, I; Volpi, G; Würthwein, F; Wagner, P; Wagner, R G; Wagner, R L; Wagner, J; Wagner, W; Wallny, R; Wang, S M; Warburton, A; Waschke, S; Waters, D; Weinberger, M; Wester, W C; Whitehouse, B; Whiteson, D; Wicklund, A B; Wicklund, E; Williams, G; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, C; Wright, T; Wu, X; Wynne, S M; Yagil, A; Yamamoto, K; Yamaoka, J; Yamashita, T; Yang, C; Yang, U K; Yang, Y C; Yao, W M; Yeh, G P; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanello, L; Zanetti, A; Zaw, I; Zhang, X; Zhou, J; Zucchelli, S

2007-03-23

We report a measurement of the Lambda b0 lifetime in the exclusive decay Lambda b0-->J/psi Lambda 0 in pp collisions at square root s=1.96 TeV using an integrated luminosity of 1.0 fb-1 of data collected by the CDF II detector at the Fermilab Tevatron. Using fully reconstructed decays, we measure tau(Lambda b0)=1.593(-0.078)(+0.083)(stat)+/-0.033(syst) ps. This is the single most precise measurement of tau(Lambda b0) and is 3.2sigma higher than the current world average.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Argondizzo, Adam; Cui, Xuefeng; Wang, Cong

We investigate the spectroscopy and photoinduced electron dynamics within the conduction band of reduced rutile TiO2(110) surface by multiphoton photoemission (mPP) spectroscopy with wavelength tunable ultrafast (!20 fs) laser pulse excitation. Tuning the mPP photon excitation energy between 2.9 and 4.6 eV reveals a nearly degenerate pair of new unoccupied states located at 2.73 ± 0.05 and 2.85 ± 0.05 eV above the Fermi level, which can be analyzed through the polarization and sample azimuthal orientation dependence of the mPP spectra. Based on the calculated electronic structure and optical transition moments, as well as related spectroscopic evidence, we assign thesemore » resonances to transitions between Ti 3d bands of nominally t2g and eg symmetry, which are split by crystal field. The initial states for the optical transition are the reduced Ti3+ states of t2g symmetry populated by formation oxygen vacancy defects, which exist within the band gap of TiO2. Furthermore,we studied the electron dynamics within the conduction band of TiO2 by three-dimensional time-resolved pump-probe interferometric mPP measurements. The spectroscopic and time-resolved studies reveal competition between 2PP and 3PP processes where the t2g-eg transitions in the 2PP process saturate, and are overtaken by the 3PP process initiated by the band-gap excitation from the valence band of TiO2.« less

Making Home Sweet and Sturdy: Toxoplasma gondii ppGalNAc-Ts Glycosylate in Hierarchical Order and Confer Cyst Wall Rigidity

PubMed Central

Tomita, Tadakimi; Sugi, Tatsuki; Yakubu, Rama; Tu, Vincent; Ma, Yanfen

2017-01-01

ABSTRACT The protozoan intracellular parasite Toxoplasma gondii forms latent cysts in the central nervous system (CNS) and persists for the lifetime of the host. This cyst is cloaked with a glycosylated structure called the cyst wall. Previously, we demonstrated that a mucin-like glycoprotein, CST1, localizes to the cyst wall and confers structural rigidity on brain cysts in a mucin-like domain-dependent manner. The mucin-like domain of CST1 is composed of 20 units of threonine-rich tandem repeats that are O-GalNAc glycosylated. A family of enzymes termed polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-Ts) initiates O-GalNAc glycosylation. To identify which isoforms of ppGalNAc-Ts are responsible for the glycosylation of the CST1 mucin-like domain and to evaluate the function of each ppGalNAc-T in the overall glycosylation of the cyst wall, all five ppGalNAc-T isoforms were deleted individually from the T. gondii genome. The ppGalNAc-T2 and -T3 deletion mutants produced various glycosylation defects on the cyst wall, implying that many cyst wall glycoproteins are glycosylated by T2 and T3. Both T2 and T3 glycosylate the CST1 mucin-like domain, and this glycosylation is necessary for CST1 to confer structural rigidity on the cyst wall. We established that T2 is required for the initial glycosylation of the mucin-like domain and that T3 is responsible for the sequential glycosylation on neighboring acceptor sites, demonstrating hierarchical glycosylation by two distinct initiating and filling-in ppGalNAc-Ts in an intact organism. PMID:28074022

Inhibition of glycogen synthase kinase-3beta downregulates total tau proteins in cultured neurons and its reversal by the blockade of protein phosphatase-2A.

PubMed

Martin, Ludovic; Magnaudeix, Amandine; Esclaire, Françoise; Yardin, Catherine; Terro, Faraj

2009-02-03

In tauopathies such as Alzheimer's disease (AD), the molecular mechanisms of tau protein aggregation into neurofibrillary tangles (NFTs) and their contribution to neurodegeneration remain not understood. It was recently demonstrated that tau, regardless of its aggregation, might represent a key mediator of neurodegeneration. Therefore, reduction of tau levels might represent a mechanism of neuroprotection. Glycogen synthase kinase-3beta (GSK3beta) and protein phosphatase-2A (PP2A) are key enzymes involved in the regulation of tau phosphorylation, and have been suggested to be involved in the abnormal tau phosphorylation and aggregation in AD. Connections between PP2A and GSK3beta signaling have been reported. We have previously demonstrated that exposure of cultured cortical neurons to lithium decreased tau protein expression and provided neuroprotection against Abeta. Since lithium is not a specific inhibitor of GSK3beta (ID50=2.0 mM), whether or not the lithium-induced tau decrease involves GSK3beta remained to be determined. For that purpose, cultured cortical neurons were exposed to 6-bromo-indirubin-3'-oxime (6-BIO), a more selective and potent GSK3beta inhibitor (ID50=1.5 microM) or to lithium. Analysis of tau levels and phosphorylation by western-blot assays showed that lithium and 6-BIO dose-dependently decreased both tau protein levels and tau phosphorylation. Conversely, inhibition of cyclin-dependent kinase-5 (CDK5) by roscovitine decreased phosphorylated tau but failed to alter tau protein levels. These data indicate that GSK3beta might be selectively involved in the regulation of tau protein levels. Moreover, inhibition of PP2A by okadaic acid, but not that of PP2B (protein phosphatase-2B)/calcineurin by FK506, dose-dependently reversed lithium-induced tau decrease. These data indicate that GSK3beta regulates both tau phosphorylation and total tau levels through PP2A.

X-linked microtubule-associated protein, Mid1, regulates axon development

PubMed Central

Lu, Tingjia; Chen, Renchao; Cox, Timothy C.; Moldrich, Randal X.; Kurniawan, Nyoman; Tan, Guohe; Perry, Jo K.; Ashworth, Alan; Bartlett, Perry F.; Xu, Li; Zhang, Jing; Lu, Bin; Wu, Mingyue; Shen, Qi; Liu, Yuanyuan; Richards, Linda J.; Xiong, Zhiqi

2013-01-01

Opitz syndrome (OS) is a genetic neurological disorder. The gene responsible for the X-linked form of OS, Midline-1 (MID1), encodes an E3 ubiquitin ligase that regulates the degradation of the catalytic subunit of protein phosphatase 2A (PP2Ac). However, how Mid1 functions during neural development is largely unknown. In this study, we provide data from in vitro and in vivo experiments suggesting that silencing Mid1 in developing neurons promotes axon growth and branch formation, resulting in a disruption of callosal axon projections in the contralateral cortex. In addition, a similar phenotype of axonal development was observed in the Mid1 knockout mouse. This defect was largely due to the accumulation of PP2Ac in Mid1-depleted cells as further down-regulation of PP2Ac rescued the axonal phenotype. Together, these data demonstrate that Mid1-dependent PP2Ac turnover is important for normal axonal development and that dysregulation of this process may contribute to the underlying cause of OS. PMID:24194544

X-linked microtubule-associated protein, Mid1, regulates axon development.

PubMed

Lu, Tingjia; Chen, Renchao; Cox, Timothy C; Moldrich, Randal X; Kurniawan, Nyoman; Tan, Guohe; Perry, Jo K; Ashworth, Alan; Bartlett, Perry F; Xu, Li; Zhang, Jing; Lu, Bin; Wu, Mingyue; Shen, Qi; Liu, Yuanyuan; Richards, Linda J; Xiong, Zhiqi

2013-11-19

Opitz syndrome (OS) is a genetic neurological disorder. The gene responsible for the X-linked form of OS, Midline-1 (MID1), encodes an E3 ubiquitin ligase that regulates the degradation of the catalytic subunit of protein phosphatase 2A (PP2Ac). However, how Mid1 functions during neural development is largely unknown. In this study, we provide data from in vitro and in vivo experiments suggesting that silencing Mid1 in developing neurons promotes axon growth and branch formation, resulting in a disruption of callosal axon projections in the contralateral cortex. In addition, a similar phenotype of axonal development was observed in the Mid1 knockout mouse. This defect was largely due to the accumulation of PP2Ac in Mid1-depleted cells as further down-regulation of PP2Ac rescued the axonal phenotype. Together, these data demonstrate that Mid1-dependent PP2Ac turnover is important for normal axonal development and that dysregulation of this process may contribute to the underlying cause of OS.

Motor development of infants with positional plagiocephaly.

PubMed

Kennedy, Eileen; Majnemer, Annette; Farmer, Jean-Pierre; Barr, Ronald G; Platt, Robert W

2009-01-01

Concurrent with recommendations to place infants to sleep in supine, there has been a dramatic increase in the number of infants with positional plagiocephaly (PP). Recent evidence suggests that infants who have decreased exposure to prone position may have a higher incidence of PP and may be at risk for a delay in the acquisition of certain motor skills. The purpose of this study was to compare motor development between infants with PP and matched peers without PP. We also examined differences in infant positioning practices when asleep and awake between the two groups. Twenty-seven infants with PP, 3 to 8 months of age, were matched by age, gender, and race to infants without PP. Motor performance was evaluated using the Alberta Infant Motor Scale (AIMS) and the Peabody Developmental Motor Scales (PDMS). Parents completed a diary that recorded infant positioning over a 3-day period. Mean AIMS percentile score for infants with PP was 31.1 +/- 21.6 as compared with 42.7 +/- 20.2 in infants without PP (p = .06). Better performance on the AIMS was positively correlated with the amount of time in prone position when awake, for both groups of children (PP r = .52, no PP r = .44, p < .05). Therapists should be aware of a risk of a motor delay when evaluating infants with PP. It is also important for parents to be informed about the importance of supervised prone playtime to enhance the development of early motor skills.

Excessive pulse pressure response to standing in community population with orthostatic systolic hypertension.

PubMed

Xu, Jingsong; Zhou, Yueying; Cao, Kaiwu; Li, Juxiang; Tao, Xuehua; Zhang, Zhihong; Liu, Xin; Liu, Jiaqi; Su, Hai

2014-03-01

The postural change of pulse pressure (PP) in the persons with orthostatic hypertension (OHT) is unclear. This study included 2849 (65.0 ± 9.3 years) community participants. Blood pressures (BPs) in supine and standing positions were measured. The differences between upright and supine BP and PP were recorded as ΔBP and ΔPP. The criteria for OHT was ΔBP ≥10 mm Hg, for orthostatic hypotension (OH) was ≤-10 mm Hg and for orthostatic normotension (ONT) was -9 to 9 mm Hg. Fasting blood lipids and glucose were measured. The supine SBP of the sOHT group were similar to that of sONT group (140.9 ± 20.2 mm Hg vs 138.2 ± 19.7 mm Hg), but significantly lower than that of sOH group (151.9 ± 19.2 mm Hg; P < .05). Their PPs were 65.3 ± 15.9, 62.8 ± 14.7, and 71.1 ± 15.1 mm Hg, respectively, and with the similar group difference like SBP. When the position changed from supine to standing, the sOHT group showed PP rise, while sOH and sONT groups showed PP reduction (3.8 ± 7.1 mm Hg vs -17.0 ± 8.5 mm Hg and -5.8 ± 6.6 mm Hg; both P < .05). Thus, the standing PP in the sOHT group was significantly higher than in the sONT (69.1 ± 18.0 mm Hg vs 57.0 ± 15.8 mm Hg; P < .05) and in the sOH (54.2 ± 15.2 mm Hg; P < .05) groups. The postural PP profile varies with the postural responses of SBP. The sOHT group has obviously increased PP and significantly higher standing PP compared with the sONT group. Copyright © 2014 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

[Effect of methylene chloride upon hepatic ischemic reperfusion injury].

PubMed

Yang, Ding-hua; Zhang, Hua; Huang, Yu; Zhou, Jie

2009-12-15

To investigate the effects and mechanisms of methylene chloride (MC) in hepatic ischemic reperfusion injury. Eighty SD-rats were divided equally into 4 groups: control group (n = 20), donors without any treatment; CoPP group (n = 20), donors injected with CoPP (5 mg/kg, ip) at 24 h; ZnPP group (n = 20), donors injected with ZnPP (20 mg/kg, ip) at 24 h; MC group (n = 20), donors fed with MC (500 mg/kg) per day for 7 days before graft procurement. Syngeneic orthotopic liver transplantation was performed in rats with modified Kamada's two-cuff technique. And SD rats were used as donors (n = 10)and recipients respectively. 5 recipients in each group were sacrificed and the grafts were procured at day 3 after transplantation, the post-operative survival time was observed in the remnant. The tests were determined as following: the level of serum ALT, AST in recipients; heme oxygenase-1 (HO-1) expression of graft was tested by immunohistochemistry and Western blot; the index of graft apoptosis examined by TUNEL method; the pathology of graft assessed by Suzuki's criteria. The level of serum ALT [(65 +/- 28) U/L], AST [(187 +/- 43) U/L] in CoPP and ALT [(75 +/- 16) U/L], AST [(185 +/- 42) U/L] in MC group was significantly lower than that ALT [(346 +/- 45) U/L], AST [(474 +/- 90) U/L] in control group and ALT [(578 +/- 75) U/L], AST [(1084 +/- 128) U/L] in ZnPP group (P < 0.01). The median expression of HO-1 in MC group was no significantly different with that in control group (P > 0.05). While the median expression of HO-1 in CoPP group was higher than that in control group (P < 0.05). The index of graft apoptosis in MC group and CoPP group, 4.1% +/- 0.6% and 3.2% +/- 0.8% respectively, was significantly lower than that (12.5% +/- 2.4%) in control group and (25.8% +/- 3.1%) in ZnPP group (P < 0.05). Compared with the other two groups, MC and CoPP groups had lesser neutrophil infiltration and a lower grade of hepatocytic injury in grafts. Suzuki's scores in grafts of MC and CoPP groups were lower than that in control and ZnPP groups (P < 0.05). The median post-transplantation survival time of the recipients in MC and CoPP groups was 100 and 93 days respectively while that in control and ZnPP groups was 85 and 12 days (P < 0.05). Over-expression of HO-1 and MC both have protective effects in hepatic ischemic reperfusion injury.

New Pyrazolopyrimidine Inhibitors of Protein Kinase D as Potent Anticancer Agents for Prostate Cancer Cells

PubMed Central

Tandon, Manuj; Johnson, James; Li, Zhihong; Xu, Shuping; Wipf, Peter; Wang, Qiming Jane

2013-01-01

The emergence of protein kinase D (PKD) as a potential therapeutic target for several diseases including cancer has triggered the search for potent, selective, and cell-permeable small molecule inhibitors. In this study, we describe the identification, in vitro characterization, structure-activity analysis, and biological evaluation of a novel PKD inhibitory scaffold exemplified by 1-naphthyl PP1 (1-NA-PP1). 1-NA-PP1 and IKK-16 were identified as pan-PKD inhibitors in a small-scale targeted kinase inhibitor library assay. Both screening hits inhibited PKD isoforms at about 100 nM and were ATP-competitive inhibitors. Analysis of several related kinases indicated that 1-NA-PP1 was highly selective for PKD as compared to IKK-16. SAR analysis showed that 1-NA-PP1 was considerably more potent and showed distinct substituent effects at the pyrazolopyrimidine core. 1-NA-PP1 was cell-active, and potently blocked prostate cancer cell proliferation by inducing G2/M arrest. It also potently blocked the migration and invasion of prostate cancer cells, demonstrating promising anticancer activities on multiple fronts. Overexpression of PKD1 or PKD3 almost completely reversed the growth arrest and the inhibition of tumor cell invasion caused by 1-NA-PP1, indicating that its anti-proliferative and anti-invasive activities were mediated through the inhibition of PKD. Interestingly, a 12-fold increase in sensitivity to 1-NA-PP1 could be achieved by engineering a gatekeeper mutation in the active site of PKD1, suggesting that 1-NA-PP1 could be paired with the analog-sensitive PKD1M659G for dissecting PKD-specific functions and signaling pathways in various biological systems. PMID:24086585

Transfusion of Plasma Collected at Late Phase after Preconditioning Reduces Myocardial Infarct Size Induced by Ischemia-reperfusion in Rats In vivo.

PubMed

Zhao, Yang; Zheng, Zhi-Nan; Cheung, Chi-Wai; Zuo, Zhi-Yi; Jin, San-Qing

2017-02-05

Plasma transfusion is a common clinical practice. Remote ischemic preconditioning (RIPC) protects organs against ischemia-reperfusion (IR) injury. Whether preconditioned plasma (PP), collected at late phase after RIPC, could protect organs against IR injury in vivo is unknown. This study explored whether transfusion of PP could reduce myocardial infarct size (IS) after IR in rat in vivo. Eighty Lewis rats were randomized to eight groups (n = 10 for each group). Two groups of plasma donor rats donated plasma at 48 h after transient limb ischemia (PP) or control protocol (nonpreconditioned plasma [NPP]). Six groups of recipient rats received normal saline (NS; NS-IR 1, and NS-IR 24 groups), NPP (NPP-IR 1 and NPP-IR 24 groups), or PP (PP-IR 1 and PP-IR 24 groups) at one or 24 h before myocardial IR. Myocardial IR consisted of 30-min left anterior descending (LAD) coronary artery occlusion and 180-min reperfusion. The area at risk (AAR) and infarct area were determined by double-staining with Evans blue and triphenyltetrazolium chloride. IS was calculated by infarct area divided by AAR. This was a 3 × 2 factorial design study, and factorial analysis was used to evaluate the data. If an interaction between the fluid and transfusion time existed, one-way analysis of variance with Bonferroni correction for multiple comparisons was used to analyze the single effects of fluid type when the transfusion time was fixed. IS in the NPP-IR 1 and PP-IR 1 groups was smaller than in the NS-IR 1 group (F = 6.838, P = 0.005; NPP-IR 1: 57 ± 8% vs. NS-IR1: 68 ± 6%, t = 2.843, P = 0.020; PP-IR 1: 56 ± 8% vs. NS-IR 1: 68 ± 6%, t = 3.102, P = 0.009), but no significant difference was detected between the NPP-IR 1 and PP-IR 1 groups (57 ± 8% vs. 56 ± 8%, t = 0.069, P = 1.000). IS in the NPP-IR 24 and PP-IR 24 groups was smaller than in the NS-IR 24 group (F = 24.796, P< 0.001; NPP-IR 24: 56% ± 7% vs. NS-IR 24: 68 ± 7%, t = 3.102, P = 0.026; PP-IR 24: 40 ± 9% vs. NS-IR 24: 68 ± 7%, t = 7.237, P< 0.001); IS in the PP-IR 24 group was smaller than in the NPP-IR 24 group (40 ± 9% vs. 56 ± 7%, t = 4.135, P = 0.002). Transfusion of PP collected at late phase after remote ischemic preconditioning could reduce IS, suggesting that late-phase cardioprotection was transferable in vivo.

Aurora kinases and protein phosphatase 1 mediate chromosome congression through regulation of CENP-E

PubMed Central

Kim, Yumi; Holland, Andrew J.; Lan, Weijie; Cleveland, Don W.

2010-01-01

Summary Opposing roles of Aurora kinases and protein phosphatase 1 (PP1) during mitosis have long been suggested. Here we demonstrate that Aurora kinases A and B phosphorylate a single residue on the kinetochore motor CENP-E. PP1 binds CENP-E via a motif overlapping this phosphorylation site and binding is disrupted by Aurora phosphorylation. Phosphorylation of CENP-E by the Auroras is enriched at spindle poles, disrupting binding of PP1 and reducing CENP-E’s affinity for individual microtubules. This phosphorylation is required for CENP-E-mediated towing of initially polar chromosomes toward the cell center. Kinetochores on such chromosomes cannot make subsequent stable attachment to spindle microtubules when dephosphorylation of CENP-E or rebinding of PP1 to CENP-E is blocked. Thus, an Aurora/PP1 phosphorylation switch modulates CENP-E motor activity as an essential feature of chromosome congression from poles and localized PP1 delivery by CENP-E to the outer kinetochore is necessary for stable microtubule capture by those chromosomes. PMID:20691903

Risk factors that affect reproductive target achievement in fertile dairy cows.

PubMed

Aungier, S P M; Roche, J F; Diskin, M G; Crowe, M A

2014-01-01

The aims of the present study were to investigate (1) the risk factors that influence the achievement of reproductive targets postpartum (pp) and (2) the key factors that influence pregnancy rate following first artificial insemination (AI) in dairy cows. Ninety-eight Holstein-Friesian pp cows were blood sampled from wk 1 to 4 pp for hematology and biochemistry. Reproductive tract health was assessed weekly by ultrasonography and vaginal mucus scoring. Body condition score (BCS), lameness score, and milk yield were assessed every 2 wk. Milk samples for progesterone assay were collected twice weekly and on d 4, 5, and 7 after AI. Risk factors associated with achieving reproductive targets depended on (1) increased metabolic activity of the liver (increased glutamate dehydrogenase at calving and increased γ-glutamyl transpeptidase in wk 4), (2) a competent immune system (increased neutrophils in wk 1; decreased α1-acid glycoprotein in wk 1, 2, and 3), (3) an endocrine system that was capable of responding by producing sufficient triiodothyronine in wk 2 and increased insulin-like growth factor I in wk 3 and 4, (4) a lower negative energy balance status (decreased nonesterified fatty acid concentration in wk 1; decreased β-hydroxybutyrate concentration in wk 2; BCS loss between calving and d 28 pp <0.5), (5) good reproductive tract health [normal uterine scan at d 45 pp; clear vaginal mucus discharge at first ovulation and at d 45 pp; resumed ovarian cyclicity by the end of the voluntary waiting period (≥ d 35 pp)], and (6) adequate diet (to ensure increased glutathione peroxidase in wk 2 and 3 and increased magnesium in wk 4). Risk factors that increased the odds of a successful first AI were previous ovulation(s) (odds ratio=3.17 per ovulation), BCS >2.5 at AI (odds ratio=3.01), and clear vaginal mucus (score=0) compared with purulent mucus (score >0) 4 d after first AI (odds ratio=2.99). In conclusion, this study identified key risk factors in the early pp period that give a higher probability of cows achieving their reproductive targets and of having a first-AI pregnancy. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Physical performance and muscle strength in older patients with and without diabetes from a public hospital in Lima, Peru.

PubMed

Palacios-Chávez, Milenka; Dejo-Seminario, Christine; Mayta-Tristán, Percy

2016-05-01

To assess the relationship between physical performance (PP) and muscle strength (MS) in elderly subjects with and without diabetes in a public hospital of Lima, Peru. A cross-sectional analysis of subjects aged 60 years or older with and without diabetes. MS was measured with a handheld dynamometer, and PP with the «timed get-up-and-go» test. Nutritional status was determined using body mass index, body fat percentage measured with a handheld fat loss monitor and protein intake based on the 24-hour recall. Age, sex, and history of hospitalization and supplementation were also recorded. The association was assessed using adjusted prevalence ratios. Overall, 139 patients with diabetes (26.6% with low PP and 13.7% with decreased MS) and 382 subjects without diabetes (36.6% with low PP and 23.0% with decreased MS) were evaluated. No association was found between T2DM and MS (aPR: 0.99; 95% CI: 0.67-1.57) or PP (aPR: 1.13; 95% CI: 0.84-1.52). Protein and supplement consumption was also unrelated (P>.05); however, history of hospitalization, age, sex, nutritional status, and body fat percentage were related (P>.05). No association was found between T2DM, MS, and PP. However, low PP was associated to female sex and overweight/obesity, and decreased MS was associated to high body fat percentage and underweight. Moreover, MS and PP were related to older age and history of hospitalization. Copyright © 2016 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

Jet properties in PbPb and pp collisions at √{s_{NN}}=5.02 TeV

NASA Astrophysics Data System (ADS)

Sirunyan, A. M.; Tumasyan, A.; Adam, W.; Ambrogi, F.; Asilar, E.; Bergauer, T.; Brandstetter, J.; Brondolin, E.; Dragicevic, M.; Erö, J.; Escalante Del Valle, A.; Flechl, M.; Friedl, M.; Frühwirth, R.; Ghete, V. M.; Hrubec, J.; Jeitler, M.; Krammer, N.; Krätschmer, I.; Liko, D.; Madlener, T.; Mikulec, I.; Rad, N.; Rohringer, H.; Schieck, J.; Schöfbeck, R.; Spanring, M.; Spitzbart, D.; Taurok, A.; Waltenberger, W.; Wittmann, J.; Wulz, C.-E.; Zarucki, M.; Chekhovsky, V.; Mossolov, V.; Suarez Gonzalez, J.; De Wolf, E. A.; Di Croce, D.; Janssen, X.; Lauwers, J.; Pieters, M.; Van De Klundert, M.; Van Haevermaet, H.; Van Mechelen, P.; Van Remortel, N.; Abu Zeid, S.; Blekman, F.; D'Hondt, J.; De Bruyn, I.; De Clercq, J.; Deroover, K.; Flouris, G.; Lontkovskyi, D.; Lowette, S.; Marchesini, I.; Moortgat, S.; Moreels, L.; Python, Q.; Skovpen, K.; Tavernier, S.; Van Doninck, W.; Van Mulders, P.; Van Parijs, I.; Beghin, D.; Bilin, B.; Brun, H.; Clerbaux, B.; De Lentdecker, G.; Delannoy, H.; Dorney, B.; Fasanella, G.; Favart, L.; Goldouzian, R.; Grebenyuk, A.; Kalsi, A. K.; Lenzi, T.; Luetic, J.; Seva, T.; Starling, E.; Vander Velde, C.; Vanlaer, P.; Vannerom, D.; Yonamine, R.; Cornelis, T.; Dobur, D.; Fagot, A.; Gul, M.; Khvastunov, I.; Poyraz, D.; Roskas, C.; Trocino, D.; Tytgat, M.; Verbeke, W.; Vermassen, B.; Vit, M.; Zaganidis, N.; Bakhshiansohi, H.; Bondu, O.; Brochet, S.; Bruno, G.; Caputo, C.; Caudron, A.; David, P.; De Visscher, S.; Delaere, C.; Delcourt, M.; Francois, B.; Giammanco, A.; Krintiras, G.; Lemaitre, V.; Magitteri, A.; Mertens, A.; Musich, M.; Piotrzkowski, K.; Quertenmont, L.; Saggio, A.; Vidal Marono, M.; Wertz, S.; Zobec, J.; Aldá Júnior, W. L.; Alves, F. L.; Alves, G. A.; Brito, L.; Correia Silva, G.; Hensel, C.; Moraes, A.; Pol, M. E.; Rebello Teles, P.; Belchior Batista Das Chagas, E.; Carvalho, W.; Chinellato, J.; Coelho, E.; Da Costa, E. M.; Da Silveira, G. G.; De Jesus Damiao, D.; Fonseca De Souza, S.; Malbouisson, H.; Medina Jaime, M.; Melo De Almeida, M.; Mora Herrera, C.; Mundim, L.; Nogima, H.; Sanchez Rosas, L. J.; Santoro, A.; Sznajder, A.; Thiel, M.; Tonelli Manganote, E. J.; Torres Da Silva De Araujo, F.; Vilela Pereira, A.; Ahuja, S.; Bernardes, C. A.; Calligaris, L.; Fernandez Perez Tomei, T. R.; Gregores, E. M.; Mercadante, P. G.; Novaes, S. F.; Padula, Sandra S.; Romero Abad, D.; Ruiz Vargas, J. C.; Aleksandrov, A.; Hadjiiska, R.; Iaydjiev, P.; Marinov, A.; Misheva, M.; Rodozov, M.; Shopova, M.; Sultanov, G.; Dimitrov, A.; Litov, L.; Pavlov, B.; Petkov, P.; Fang, W.; Gao, X.; Yuan, L.; Ahmad, M.; Bian, J. G.; Chen, G. M.; Chen, H. S.; Chen, M.; Chen, Y.; Jiang, C. H.; Leggat, D.; Liao, H.; Liu, Z.; Romeo, F.; Shaheen, S. M.; Spiezia, A.; Tao, J.; Wang, C.; Wang, Z.; Yazgan, E.; Zhang, H.; Zhao, J.; Ban, Y.; Chen, G.; Li, J.; Li, Q.; Liu, S.; Mao, Y.; Qian, S. J.; Wang, D.; Xu, Z.; Wang, Y.; Avila, C.; Cabrera, A.; Carrillo Montoya, C. A.; Chaparro Sierra, L. F.; Florez, C.; González Hernández, C. F.; Segura Delgado, M. A.; Courbon, B.; Godinovic, N.; Lelas, D.; Puljak, I.; Sculac, T.; Antunovic, Z.; Kovac, M.; Brigljevic, V.; Ferencek, D.; Kadija, K.; Mesic, B.; Starodumov, A.; Susa, T.; Ather, M. W.; Attikis, A.; Mavromanolakis, G.; Mousa, J.; Nicolaou, C.; Ptochos, F.; Razis, P. A.; Rykaczewski, H.; Finger, M.; Finger, M.; Carrera Jarrin, E.; Ellithi Kamel, A.; Mahmoud, M. A.; Mohammed, Y.; Bhowmik, S.; Dewanjee, R. K.; Kadastik, M.; Perrini, L.; Raidal, M.; Veelken, C.; Eerola, P.; Kirschenmann, H.; Pekkanen, J.; Voutilainen, M.; Havukainen, J.; Heikkilä, J. K.; Järvinen, T.; Karimäki, V.; Kinnunen, R.; Lampén, T.; Lassila-Perini, K.; Laurila, S.; Lehti, S.; Lindén, T.; Luukka, P.; Mäenpää, T.; Siikonen, H.; Tuominen, E.; Tuominiemi, J.; Tuuva, T.; Besancon, M.; Couderc, F.; Dejardin, M.; Denegri, D.; Faure, J. L.; Ferri, F.; Ganjour, S.; Ghosh, S.; Givernaud, A.; Gras, P.; Hamel de Monchenault, G.; Jarry, P.; Leloup, C.; Locci, E.; Machet, M.; Malcles, J.; Negro, G.; Rander, J.; Rosowsky, A.; Sahin, M. Ö.; Titov, M.; Abdulsalam, A.; Amendola, C.; Antropov, I.; Baffioni, S.; Beaudette, F.; Busson, P.; Cadamuro, L.; Charlot, C.; Granier de Cassagnac, R.; Jo, M.; Kucher, I.; Lisniak, S.; Lobanov, A.; Martin Blanco, J.; Nguyen, M.; Ochando, C.; Ortona, G.; Paganini, P.; Pigard, P.; Salerno, R.; Sauvan, J. B.; Sirois, Y.; Stahl Leiton, A. G.; Yilmaz, Y.; Zabi, A.; Zghiche, A.; Agram, J.-L.; Andrea, J.; Bloch, D.; Brom, J.-M.; Chabert, E. C.; Collard, C.; Conte, E.; Coubez, X.; Drouhin, F.; Fontaine, J.-C.; Gelé, D.; Goerlach, U.; Jansová, M.; Juillot, P.; Le Bihan, A.-C.; Tonon, N.; Van Hove, P.; Gadrat, S.; Beauceron, S.; Bernet, C.; Boudoul, G.; Chanon, N.; Chierici, R.; Contardo, D.; Depasse, P.; El Mamouni, H.; Fay, J.; Finco, L.; Gascon, S.; Gouzevitch, M.; Grenier, G.; Ille, B.; Lagarde, F.; Laktineh, I. B.; Lattaud, H.; Lethuillier, M.; Mirabito, L.; Pequegnot, A. L.; Perries, S.; Popov, A.; Sordini, V.; Vander Donckt, M.; Viret, S.; Zhang, S.; Toriashvili, T.; Tsamalaidze, Z.; Autermann, C.; Feld, L.; Kiesel, M. K.; Klein, K.; Lipinski, M.; Preuten, M.; Rauch, M. P.; Schomakers, C.; Schulz, J.; Teroerde, M.; Wittmer, B.; Zhukov, V.; Albert, A.; Duchardt, D.; Endres, M.; Erdmann, M.; Erdweg, S.; Esch, T.; Fischer, R.; Güth, A.; Hebbeker, T.; Heidemann, C.; Hoepfner, K.; Knutzen, S.; Merschmeyer, M.; Meyer, A.; Millet, P.; Mukherjee, S.; Pook, T.; Radziej, M.; Reithler, H.; Rieger, M.; Scheuch, F.; Teyssier, D.; Thüer, S.; Flügge, G.; Kargoll, B.; Kress, T.; Künsken, A.; Müller, T.; Nehrkorn, A.; Nowack, A.; Pistone, C.; Pooth, O.; Stahl, A.; Aldaya Martin, M.; Arndt, T.; Asawatangtrakuldee, C.; Babounikau, I.; Beernaert, K.; Behnke, O.; Behrens, U.; Bermúdez Martínez, A.; Bertsche, D.; Bin Anuar, A. A.; Borras, K.; Botta, V.; Campbell, A.; Connor, P.; Contreras-Campana, C.; Costanza, F.; Danilov, V.; De Wit, A.; Diez Pardos, C.; Domínguez Damiani, D.; Eckerlin, G.; Eckstein, D.; Eichhorn, T.; Elwood, A.; Eren, E.; Gallo, E.; Geiser, A.; Grados Luyando, J. M.; Grohsjean, A.; Gunnellini, P.; Guthoff, M.; Harb, A.; Hauk, J.; Jung, H.; Kasemann, M.; Keaveney, J.; Kleinwort, C.; Knolle, J.; Krücker, D.; Lange, W.; Lelek, A.; Lenz, T.; Lipka, K.; Lohmann, W.; Mankel, R.; Melzer-Pellmann, I.-A.; Meyer, A. B.; Meyer, M.; Missiroli, M.; Mittag, G.; Mnich, J.; Mussgiller, A.; Pflitsch, S. K.; Pitzl, D.; Raspereza, A.; Savitskyi, M.; Saxena, P.; Schwanenberger, C.; Shevchenko, R.; Singh, A.; Stefaniuk, N.; Tholen, H.; Van Onsem, G. P.; Walsh, R.; Wen, Y.; Wichmann, K.; Wissing, C.; Zenaiev, O.; Aggleton, R.; Bein, S.; Blobel, V.; Centis Vignali, M.; Dreyer, T.; Garutti, E.; Gonzalez, D.; Haller, J.; Hinzmann, A.; Hoffmann, M.; Karavdina, A.; Kasieczka, G.; Klanner, R.; Kogler, R.; Kovalchuk, N.; Kurz, S.; Kutzner, V.; Lange, J.; Marconi, D.; Multhaup, J.; Niedziela, M.; Nowatschin, D.; Peiffer, T.; Perieanu, A.; Reimers, A.; Scharf, C.; Schleper, P.; Schmidt, A.; Schumann, S.; Schwandt, J.; Sonneveld, J.; Stadie, H.; Steinbrück, G.; Stober, F. M.; Stöver, M.; Troendle, D.; Usai, E.; Vanhoefer, A.; Vormwald, B.; Akbiyik, M.; Barth, C.; Baselga, M.; Baur, S.; Butz, E.; Caspart, R.; Chwalek, T.; Colombo, F.; De Boer, W.; Dierlamm, A.; Faltermann, N.; Freund, B.; Friese, R.; Giffels, M.; Harrendorf, M. A.; Hartmann, F.; Heindl, S. M.; Husemann, U.; Kassel, F.; Kudella, S.; Mildner, H.; Mozer, M. U.; Müller, Th.; Plagge, M.; Quast, G.; Rabbertz, K.; Schröder, M.; Shvetsov, I.; Sieber, G.; Simonis, H. J.; Ulrich, R.; Wayand, S.; Weber, M.; Weiler, T.; Williamson, S.; Wöhrmann, C.; Wolf, R.; Anagnostou, G.; Daskalakis, G.; Geralis, T.; Kyriakis, A.; Loukas, D.; Topsis-Giotis, I.; Karathanasis, G.; Kesisoglou, S.; Panagiotou, A.; Saoulidou, N.; Tziaferi, E.; Vellidis, K.; Kousouris, K.; Papakrivopoulos, I.; Evangelou, I.; Foudas, C.; Gianneios, P.; Katsoulis, P.; Kokkas, P.; Mallios, S.; Manthos, N.; Papadopoulos, I.; Paradas, E.; Strologas, J.; Triantis, F. A.; Tsitsonis, D.; Csanad, M.; Filipovic, N.; Pasztor, G.; Surányi, O.; Veres, G. I.; Bencze, G.; Hajdu, C.; Horvath, D.; Hunyadi, Á.; Sikler, F.; Veszpremi, V.; Vesztergombi, G.; Vámi, T. Á.; Beni, N.; Czellar, S.; Karancsi, J.; Makovec, A.; Molnar, J.; Szillasi, Z.; Bartók, M.; Raics, P.; Trocsanyi, Z. L.; Ujvari, B.; Choudhury, S.; Komaragiri, J. R.; Bahinipati, S.; Mal, P.; Mandal, K.; Nayak, A.; Sahoo, D. K.; Swain, S. K.; Bansal, S.; Beri, S. B.; Bhatnagar, V.; Chauhan, S.; Chawla, R.; Dhingra, N.; Gupta, R.; Kaur, A.; Kaur, M.; Kaur, S.; Kumar, R.; Kumari, P.; Lohan, M.; Mehta, A.; Sharma, S.; Singh, J. B.; Walia, G.; Kumar, Ashok; Shah, Aashaq; Bhardwaj, A.; Choudhary, B. C.; Garg, R. B.; Keshri, S.; Kumar, A.; Malhotra, S.; Naimuddin, M.; Ranjan, K.; Sharma, R.; Bhardwaj, R.; Bhattacharya, R.; Bhattacharya, S.; Bhawandeep, U.; Bhowmik, D.; Dey, S.; Dutt, S.; Dutta, S.; Ghosh, S.; Majumdar, N.; Mondal, K.; Mukhopadhyay, S.; Nandan, S.; Purohit, A.; Rout, P. K.; Roy, A.; Roy Chowdhury, S.; Sarkar, S.; Sharan, M.; Singh, B.; Thakur, S.; Behera, P. K.; Chudasama, R.; Dutta, D.; Jha, V.; Kumar, V.; Mohanty, A. K.; Netrakanti, P. K.; Pant, L. M.; Shukla, P.; Topkar, A.; Aziz, T.; Dugad, S.; Mahakud, B.; Mitra, S.; Mohanty, G. B.; Ravindra Kumar Verma, R.; Sur, N.; Sutar, B.; Banerjee, S.; Bhattacharya, S.; Chatterjee, S.; Das, P.; Guchait, M.; Jain, Sa.; Kumar, S.; Maity, M.; Majumder, G.; Mazumdar, K.; Sahoo, N.; Sarkar, T.; Wickramage, N.; Chauhan, S.; Dube, S.; Hegde, V.; Kapoor, A.; Kothekar, K.; Pandey, S.; Rane, A.; Sharma, S.; Chenarani, S.; Eskandari Tadavani, E.; Etesami, S. M.; Khakzad, M.; Mohammadi Najafabadi, M.; Naseri, M.; Paktinat Mehdiabadi, S.; Rezaei Hosseinabadi, F.; Safarzadeh, B.; Zeinali, M.; Felcini, M.; Grunewald, M.; Abbrescia, M.; Calabria, C.; Colaleo, A.; Creanza, D.; Cristella, L.; De Filippis, N.; De Palma, M.; Di Florio, A.; Errico, F.; Fiore, L.; Gelmi, A.; Iaselli, G.; Lezki, S.; Maggi, G.; Maggi, M.; Marangelli, B.; Miniello, G.; My, S.; Nuzzo, S.; Pompili, A.; Pugliese, G.; Radogna, R.; Ranieri, A.; Selvaggi, G.; Sharma, A.; Silvestris, L.; Venditti, R.; Verwilligen, P.; Zito, G.; Abbiendi, G.; Battilana, C.; Bonacorsi, D.; Borgonovi, L.; Braibant-Giacomelli, S.; Brigliadori, L.; Campanini, R.; Capiluppi, P.; Castro, A.; Cavallo, F. R.; Chhibra, S. S.; Codispoti, G.; Cuffiani, M.; Dallavalle, G. M.; Fabbri, F.; Fanfani, A.; Fasanella, D.; Giacomelli, P.; Grandi, C.; Guiducci, L.; Iemmi, F.; Marcellini, S.; Masetti, G.; Montanari, A.; Navarria, F. L.; Perrotta, A.; Rovelli, T.; Siroli, G. P.; Tosi, N.; Albergo, S.; Costa, S.; Di Mattia, A.; Giordano, F.; Potenza, R.; Tricomi, A.; Tuve, C.; Barbagli, G.; Chatterjee, K.; Ciulli, V.; Civinini, C.; D'Alessandro, R.; Focardi, E.; Latino, G.; Lenzi, P.; Meschini, M.; Paoletti, S.; Russo, L.; Sguazzoni, G.; Strom, D.; Viliani, L.; Benussi, L.; Bianco, S.; Fabbri, F.; Piccolo, D.; Primavera, F.; Calvelli, V.; Ferro, F.; Ravera, F.; Robutti, E.; Tosi, S.; Benaglia, A.; Beschi, A.; Brianza, L.; Brivio, F.; Ciriolo, V.; Dinardo, M. E.; Fiorendi, S.; Gennai, S.; Ghezzi, A.; Govoni, P.; Malberti, M.; Malvezzi, S.; Manzoni, R. A.; Menasce, D.; Moroni, L.; Paganoni, M.; Pauwels, K.; Pedrini, D.; Pigazzini, S.; Ragazzi, S.; Tabarelli de Fatis, T.; Buontempo, S.; Cavallo, N.; Di Guida, S.; Fabozzi, F.; Fienga, F.; Galati, G.; Iorio, A. O. M.; Khan, W. A.; Lista, L.; Meola, S.; Paolucci, P.; Sciacca, C.; Thyssen, F.; Voevodina, E.; Azzi, P.; Bacchetta, N.; Benato, L.; Bisello, D.; Boletti, A.; Carlin, R.; Carvalho Antunes De Oliveira, A.; Checchia, P.; De Castro Manzano, P.; Dorigo, T.; Dosselli, U.; Gasparini, F.; Gasparini, U.; Gozzelino, A.; Lacaprara, S.; Margoni, M.; Meneguzzo, A. T.; Pozzobon, N.; Ronchese, P.; Rossin, R.; Simonetto, F.; Tiko, A.; Torassa, E.; Zanetti, M.; Zotto, P.; Zumerle, G.; Braghieri, A.; Magnani, A.; Montagna, P.; Ratti, S. P.; Re, V.; Ressegotti, M.; Riccardi, C.; Salvini, P.; Vai, I.; Vitulo, P.; Alunni Solestizi, L.; Biasini, M.; Bilei, G. M.; Cecchi, C.; Ciangottini, D.; Fanò, L.; Lariccia, P.; Leonardi, R.; Manoni, E.; Mantovani, G.; Mariani, V.; Menichelli, M.; Rossi, A.; Santocchia, A.; Spiga, D.; Androsov, K.; Azzurri, P.; Bagliesi, G.; Bianchini, L.; Boccali, T.; Borrello, L.; Castaldi, R.; Ciocci, M. A.; Dell'Orso, R.; Fedi, G.; Giannini, L.; Giassi, A.; Grippo, M. T.; Ligabue, F.; Lomtadze, T.; Manca, E.; Mandorli, G.; Messineo, A.; Palla, F.; Rizzi, A.; Spagnolo, P.; Tenchini, R.; Tonelli, G.; Venturi, A.; Verdini, P. G.; Barone, L.; Cavallari, F.; Cipriani, M.; Daci, N.; Del Re, D.; Di Marco, E.; Diemoz, M.; Gelli, S.; Longo, E.; Marzocchi, B.; Meridiani, P.; Organtini, G.; Pandolfi, F.; Paramatti, R.; Preiato, F.; Rahatlou, S.; Rovelli, C.; Santanastasio, F.; Amapane, N.; Arcidiacono, R.; Argiro, S.; Arneodo, M.; Bartosik, N.; Bellan, R.; Biino, C.; Cartiglia, N.; Castello, R.; Cenna, F.; Costa, M.; Covarelli, R.; Degano, A.; Demaria, N.; Kiani, B.; Mariotti, C.; Maselli, S.; Migliore, E.; Monaco, V.; Monteil, E.; Monteno, M.; Obertino, M. M.; Pacher, L.; Pastrone, N.; Pelliccioni, M.; Pinna Angioni, G. L.; Romero, A.; Ruspa, M.; Sacchi, R.; Shchelina, K.; Sola, V.; Solano, A.; Staiano, A.; Belforte, S.; Candelise, V.; Casarsa, M.; Cossutti, F.; Della Ricca, G.; Vazzoler, F.; Zanetti, A.; Kim, D. H.; Kim, G. N.; Kim, M. S.; Lee, J.; Lee, S.; Lee, S. W.; Moon, C. S.; Oh, Y. D.; Sekmen, S.; Son, D. C.; Yang, Y. C.; Kim, H.; Moon, D. H.; Oh, G.; Brochero Cifuentes, J. A.; Goh, J.; Kim, T. J.; Cho, S.; Choi, S.; Go, Y.; Gyun, D.; Ha, S.; Hong, B.; Jo, Y.; Kim, Y.; Lee, K.; Lee, K. S.; Lee, S.; Lim, J.; Park, S. K.; Roh, Y.; Almond, J.; Kim, J.; Kim, J. S.; Lee, H.; Lee, K.; Nam, K.; Oh, S. B.; Radburn-Smith, B. C.; Seo, S. h.; Yang, U. K.; Yoo, H. D.; Yu, G. B.; Kim, H.; Kim, J. H.; Lee, J. S. H.; Park, I. C.; Choi, Y.; Hwang, C.; Lee, J.; Yu, I.; Dudenas, V.; Juodagalvis, A.; Vaitkus, J.; Ahmed, I.; Ibrahim, Z. A.; Md Ali, M. A. B.; Mohamad Idris, F.; Wan Abdullah, W. A. T.; Yusli, M. N.; Zolkapli, Z.; Reyes-Almanza, R.; Ramirez-Sanchez, G.; Duran-Osuna, M. C.; Castilla-Valdez, H.; De La Cruz-Burelo, E.; Heredia-De La Cruz, I.; Rabadan-Trejo, R. I.; Lopez-Fernandez, R.; Mejia Guisao, J.; Sanchez-Hernandez, A.; Carrillo Moreno, S.; Oropeza Barrera, C.; Vazquez Valencia, F.; Eysermans, J.; Pedraza, I.; Salazar Ibarguen, H. A.; Uribe Estrada, C.; Morelos Pineda, A.; Krofcheck, D.; Butler, P. H.; Ahmad, A.; Ahmad, M.; Hassan, Q.; Hoorani, H. R.; Saddique, A.; Shah, M. A.; Shoaib, M.; Waqas, M.; Bialkowska, H.; Bluj, M.; Boimska, B.; Frueboes, T.; Górski, M.; Kazana, M.; Nawrocki, K.; Szleper, M.; Traczyk, P.; Zalewski, P.; Bunkowski, K.; Byszuk, A.; Doroba, K.; Kalinowski, A.; Konecki, M.; Krolikowski, J.; Misiura, M.; Olszewski, M.; Pyskir, A.; Walczak, M.; Bargassa, P.; Beirão Da Cruz E Silva, C.; Di Francesco, A.; Faccioli, P.; Galinhas, B.; Gallinaro, M.; Hollar, J.; Leonardo, N.; Lloret Iglesias, L.; Nemallapudi, M. V.; Seixas, J.; Strong, G.; Toldaiev, O.; Vadruccio, D.; Varela, J.; Afanasiev, S.; Bunin, P.; Gavrilenko, M.; Golutvin, I.; Gorbunov, I.; Kamenev, A.; Karjavin, V.; Lanev, A.; Malakhov, A.; Matveev, V.; Moisenz, P.; Palichik, V.; Perelygin, V.; Shmatov, S.; Shulha, S.; Skatchkov, N.; Smirnov, V.; Voytishin, N.; Zarubin, A.; Ivanov, Y.; Kim, V.; Kuznetsova, E.; Levchenko, P.; Murzin, V.; Oreshkin, V.; Smirnov, I.; Sosnov, D.; Sulimov, V.; Uvarov, L.; Vavilov, S.; Vorobyev, A.; Andreev, Yu.; Dermenev, A.; Gninenko, S.; Golubev, N.; Karneyeu, A.; Kirsanov, M.; Krasnikov, N.; Pashenkov, A.; Tlisov, D.; Toropin, A.; Epshteyn, V.; Gavrilov, V.; Lychkovskaya, N.; Popov, V.; Pozdnyakov, I.; Safronov, G.; Spiridonov, A.; Stepennov, A.; Stolin, V.; Toms, M.; Vlasov, E.; Zhokin, A.; Aushev, T.; Bylinkin, A.; Chadeeva, M.; Parygin, P.; Philippov, D.; Polikarpov, S.; Popova, E.; Rusinov, V.; Andreev, V.; Azarkin, M.; Dremin, I.; Kirakosyan, M.; Rusakov, S. V.; Terkulov, A.; Baskakov, A.; Belyaev, A.; Boos, E.; Ershov, A.; Gribushin, A.; Kaminskiy, A.; Kodolova, O.; Korotkikh, V.; Lokhtin, I.; Miagkov, I.; Obraztsov, S.; Petrushanko, S.; Savrin, V.; Snigirev, A.; Vardanyan, I.; Blinov, V.; Shtol, D.; Skovpen, Y.; Azhgirey, I.; Bayshev, I.; Bitioukov, S.; Elumakhov, D.; Godizov, A.; Kachanov, V.; Kalinin, A.; Konstantinov, D.; Mandrik, P.; Petrov, V.; Ryutin, R.; Sobol, A.; Troshin, S.; Tyurin, N.; Uzunian, A.; Volkov, A.; Babaev, A.; Adzic, P.; Cirkovic, P.; Devetak, D.; Dordevic, M.; Milosevic, J.; Alcaraz Maestre, J.; Bachiller, I.; Barrio Luna, M.; Cerrada, M.; Colino, N.; De La Cruz, B.; Delgado Peris, A.; Fernandez Bedoya, C.; Fernández Ramos, J. P.; Flix, J.; Fouz, M. C.; Gonzalez Lopez, O.; Goy Lopez, S.; Hernandez, J. M.; Josa, M. I.; Moran, D.; Pérez-Calero Yzquierdo, A.; Puerta Pelayo, J.; Redondo, I.; Romero, L.; Soares, M. S.; Triossi, A.; Álvarez Fernández, A.; Albajar, C.; de Trocóniz, J. F.; Cuevas, J.; Erice, C.; Fernandez Menendez, J.; Folgueras, S.; Gonzalez Caballero, I.; González Fernández, J. R.; Palencia Cortezon, E.; Sanchez Cruz, S.; Vischia, P.; Vizan Garcia, J. M.; Cabrillo, I. J.; Calderon, A.; Chazin Quero, B.; Duarte Campderros, J.; Fernandez, M.; Fernández Manteca, P. J.; Garcia-Ferrero, J.; García Alonso, A.; Gomez, G.; Lopez Virto, A.; Marco, J.; Martinez Rivero, C.; Martinez Ruiz del Arbol, P.; Matorras, F.; Piedra Gomez, J.; Prieels, C.; Rodrigo, T.; Ruiz-Jimeno, A.; Scodellaro, L.; Trevisani, N.; Vila, I.; Vilar Cortabitarte, R.; Abbaneo, D.; Akgun, B.; Auffray, E.; Baillon, P.; Ball, A. H.; Barney, D.; Bendavid, J.; Bianco, M.; Bocci, A.; Botta, C.; Camporesi, T.; Cepeda, M.; Cerminara, G.; Chapon, E.; Chen, Y.; d'Enterria, D.; Dabrowski, A.; Daponte, V.; David, A.; De Gruttola, M.; De Roeck, A.; Deelen, N.; Dobson, M.; du Pree, T.; Dünser, M.; Dupont, N.; Elliott-Peisert, A.; Everaerts, P.; Fallavollita, F.; Franzoni, G.; Fulcher, J.; Funk, W.; Gigi, D.; Gilbert, A.; Gill, K.; Glege, F.; Gulhan, D.; Hegeman, J.; Innocente, V.; Jafari, A.; Janot, P.; Karacheban, O.; Kieseler, J.; Knünz, V.; Kornmayer, A.; Krammer, M.; Lange, C.; Lecoq, P.; Lourenço, C.; Lucchini, M. T.; Malgeri, L.; Mannelli, M.; Martelli, A.; Meijers, F.; Merlin, J. A.; Mersi, S.; Meschi, E.; Milenovic, P.; Moortgat, F.; Mulders, M.; Neugebauer, H.; Ngadiuba, J.; Orfanelli, S.; Orsini, L.; Pantaleo, F.; Pape, L.; Perez, E.; Peruzzi, M.; Petrilli, A.; Petrucciani, G.; Pfeiffer, A.; Pierini, M.; Pitters, F. M.; Rabady, D.; Racz, A.; Reis, T.; Rolandi, G.; Rovere, M.; Sakulin, H.; Schäfer, C.; Schwick, C.; Seidel, M.; Selvaggi, M.; Sharma, A.; Silva, P.; Sphicas, P.; Stakia, A.; Steggemann, J.; Stoye, M.; Tosi, M.; Treille, D.; Tsirou, A.; Veckalns, V.; Verweij, M.; Zeuner, W. D.; Bertl, W.; Caminada, L.; Deiters, K.; Erdmann, W.; Horisberger, R.; Ingram, Q.; Kaestli, H. C.; Kotlinski, D.; Langenegger, U.; Rohe, T.; Wiederkehr, S. A.; Backhaus, M.; Bäni, L.; Berger, P.; Casal, B.; Chernyavskaya, N.; Dissertori, G.; Dittmar, M.; Donegà, M.; Dorfer, C.; Grab, C.; Heidegger, C.; Hits, D.; Hoss, J.; Klijnsma, T.; Lustermann, W.; Marionneau, M.; Meinhard, M. T.; Meister, D.; Micheli, F.; Musella, P.; NessiTedaldi, F.; Pata, J.; Pauss, F.; Perrin, G.; Perrozzi, L.; Quittnat, M.; Reichmann, M.; Ruini, D.; Sanz Becerra, D. A.; Schönenberger, M.; Shchutska, L.; Tavolaro, V. R.; Theofilatos, K.; Vesterbacka Olsson, M. L.; Wallny, R.; Zhu, D. H.; Aarrestad, T. K.; Amsler, C.; Brzhechko, D.; Canelli, M. F.; De Cosa, A.; Del Burgo, R.; Donato, S.; Galloni, C.; Hreus, T.; Kilminster, B.; Neutelings, I.; Pinna, D.; Rauco, G.; Robmann, P.; Salerno, D.; Schweiger, K.; Seitz, C.; Takahashi, Y.; Zucchetta, A.; Chang, Y. H.; Cheng, K. y.; Doan, T. H.; Jain, Sh.; Khurana, R.; Kuo, C. M.; Lin, W.; Pozdnyakov, A.; Yu, S. S.; Kumar, Arun; Chang, P.; Chao, Y.; Chen, K. F.; Chen, P. H.; Fiori, F.; Hou, W.-S.; Hsiung, Y.; Liu, Y. F.; Lu, R.-S.; Paganis, E.; Psallidas, A.; Steen, A.; Tsai, J. f.; Asavapibhop, B.; Kovitanggoon, K.; Singh, G.; Srimanobhas, N.; Bakirci, M. N.; Bat, A.; Boran, F.; Damarseckin, S.; Demiroglu, Z. S.; Dozen, C.; Eskut, E.; Girgis, S.; Gokbulut, G.; Guler, Y.; Hos, I.; Kangal, E. E.; Kara, O.; Kiminsu, U.; Oglakci, M.; Onengut, G.; Ozdemir, K.; Ozturk, S.; Polatoz, A.; Sunar Cerci, D.; Tok, U. G.; Turkcapar, S.; Zorbakir, I. S.; Zorbilmez, C.; Karapinar, G.; Ocalan, K.; Yalvac, M.; Zeyrek, M.; Atakisi, I. O.; Gülmez, E.; Kaya, M.; Kaya, O.; Tekten, S.; Yetkin, E. A.; Agaras, M. N.; Atay, S.; Cakir, A.; Cankocak, K.; Komurcu, Y.; Grynyov, B.; Levchuk, L.; Ball, F.; Beck, L.; Brooke, J. J.; Burns, D.; Clement, E.; Cussans, D.; Davignon, O.; Flacher, H.; Goldstein, J.; Heath, G. P.; Heath, H. F.; Kreczko, L.; Newbold, D. M.; Paramesvaran, S.; Sakuma, T.; Seif El Nasr-storey, S.; Smith, D.; Smith, V. J.; Belyaev, A.; Brew, C.; Brown, R. M.; Cieri, D.; Cockerill, D. J. A.; Coughlan, J. A.; Harder, K.; Harper, S.; Linacre, J.; Olaiya, E.; Petyt, D.; Shepherd-Themistocleous, C. H.; Thea, A.; Tomalin, I. R.; Williams, T.; Womersley, W. J.; Auzinger, G.; Bainbridge, R.; Bloch, P.; Borg, J.; Breeze, S.; Buchmuller, O.; Bundock, A.; Casasso, S.; Colling, D.; Corpe, L.; Dauncey, P.; Davies, G.; Della Negra, M.; Di Maria, R.; Haddad, Y.; Hall, G.; Iles, G.; James, T.; Komm, M.; Lane, R.; Laner, C.; Lyons, L.; Magnan, A.-M.; Malik, S.; Mastrolorenzo, L.; Matsushita, T.; Nash, J.; Nikitenko, A.; Palladino, V.; Pesaresi, M.; Richards, A.; Rose, A.; Scott, E.; Seez, C.; Shtipliyski, A.; Strebler, T.; Summers, S.; Tapper, A.; Uchida, K.; Vazquez Acosta, M.; Virdee, T.; Wardle, N.; Winterbottom, D.; Wright, J.; Zenz, S. C.; Cole, J. E.; Hobson, P. R.; Khan, A.; Kyberd, P.; Morton, A.; Reid, I. D.; Teodorescu, L.; Zahid, S.; Borzou, A.; Call, K.; Dittmann, J.; Hatakeyama, K.; Liu, H.; Pastika, N.; Smith, C.; Bartek, R.; Dominguez, A.; Buccilli, A.; Cooper, S. I.; Henderson, C.; Rumerio, P.; West, C.; Arcaro, D.; Avetisyan, A.; Bose, T.; Gastler, D.; Rankin, D.; Richardson, C.; Rohlf, J.; Sulak, L.; Zou, D.; Benelli, G.; Cutts, D.; Hadley, M.; Hakala, J.; Heintz, U.; Hogan, J. M.; Kwok, K. H. M.; Laird, E.; Landsberg, G.; Lee, J.; Mao, Z.; Narain, M.; Pazzini, J.; Piperov, S.; Sagir, S.; Syarif, R.; Yu, D.; Band, R.; Brainerd, C.; Breedon, R.; Burns, D.; Calderon De La Barca Sanchez, M.; Chertok, M.; Conway, J.; Conway, R.; Cox, P. T.; Erbacher, R.; Flores, C.; Funk, G.; Ko, W.; Lander, R.; Mclean, C.; Mulhearn, M.; Pellett, D.; Pilot, J.; Shalhout, S.; Shi, M.; Smith, J.; Stolp, D.; Taylor, D.; Tos, K.; Tripathi, M.; Wang, Z.; Zhang, F.; Bachtis, M.; Bravo, C.; Cousins, R.; Dasgupta, A.; Florent, A.; Hauser, J.; Ignatenko, M.; Mccoll, N.; Regnard, S.; Saltzberg, D.; Schnaible, C.; Valuev, V.; Bouvier, E.; Burt, K.; Clare, R.; Ellison, J.; Gary, J. W.; Ghiasi Shirazi, S. M. A.; Hanson, G.; Karapostoli, G.; Kennedy, E.; Lacroix, F.; Long, O. R.; Olmedo Negrete, M.; Paneva, M. I.; Si, W.; Wang, L.; Wei, H.; Wimpenny, S.; Yates, B. R.; Branson, J. G.; Cittolin, S.; Derdzinski, M.; Gerosa, R.; Gilbert, D.; Hashemi, B.; Holzner, A.; Klein, D.; Kole, G.; Krutelyov, V.; Letts, J.; Masciovecchio, M.; Olivito, D.; Padhi, S.; Pieri, M.; Sani, M.; Sharma, V.; Simon, S.; Tadel, M.; Vartak, A.; Wasserbaech, S.; Wood, J.; Würthwein, F.; Yagil, A.; Zevi Della Porta, G.; Amin, N.; Bhandari, R.; Bradmiller-Feld, J.; Campagnari, C.; Citron, M.; Dishaw, A.; Dutta, V.; Franco Sevilla, M.; Gouskos, L.; Heller, R.; Incandela, J.; Ovcharova, A.; Qu, H.; Richman, J.; Stuart, D.; Suarez, I.; Yoo, J.; Anderson, D.; Bornheim, A.; Bunn, J.; Lawhorn, J. M.; Newman, H. B.; Nguyen, T. Q.; Pena, C.; Spiropulu, M.; Vlimant, J. R.; Wilkinson, R.; Xie, S.; Zhang, Z.; Zhu, R. Y.; Andrews, M. B.; Ferguson, T.; Mudholkar, T.; Paulini, M.; Russ, J.; Sun, M.; Vogel, H.; Vorobiev, I.; Weinberg, M.; Cumalat, J. P.; Ford, W. T.; Jensen, F.; Johnson, A.; Krohn, M.; Leontsinis, S.; MacDonald, E.; Mulholland, T.; Stenson, K.; Ulmer, K. A.; Wagner, S. R.; Alexander, J.; Chaves, J.; Cheng, Y.; Chu, J.; Datta, A.; Mcdermott, K.; Mirman, N.; Patterson, J. R.; Quach, D.; Rinkevicius, A.; Ryd, A.; Skinnari, L.; Soffi, L.; Tan, S. M.; Tao, Z.; Thom, J.; Tucker, J.; Wittich, P.; Zientek, M.; Abdullin, S.; Albrow, M.; Alyari, M.; Apollinari, G.; Apresyan, A.; Apyan, A.; Banerjee, S.; Bauerdick, L. A. T.; Beretvas, A.; Berryhill, J.; Bhat, P. C.; Bolla, G.; Burkett, K.; Butler, J. N.; Canepa, A.; Cerati, G. B.; Cheung, H. W. K.; Chlebana, F.; Cremonesi, M.; Duarte, J.; Elvira, V. D.; Freeman, J.; Gecse, Z.; Gottschalk, E.; Gray, L.; Green, D.; Grünendahl, S.; Gutsche, O.; Hanlon, J.; Harris, R. M.; Hasegawa, S.; Hirschauer, J.; Hu, Z.; Jayatilaka, B.; Jindariani, S.; Johnson, M.; Joshi, U.; Klima, B.; Kortelainen, M. J.; Kreis, B.; Lammel, S.; Lincoln, D.; Lipton, R.; Liu, M.; Liu, T.; Lopes De Sá, R.; Lykken, J.; Maeshima, K.; Magini, N.; Marraffino, J. M.; Mason, D.; McBride, P.; Merkel, P.; Mrenna, S.; Nahn, S.; O'Dell, V.; Pedro, K.; Prokofyev, O.; Rakness, G.; Ristori, L.; Savoy-Navarro, A.; Schneider, B.; Sexton-Kennedy, E.; Soha, A.; Spalding, W. J.; Spiegel, L.; Stoynev, S.; Strait, J.; Strobbe, N.; Taylor, L.; Tkaczyk, S.; Tran, N. V.; Uplegger, L.; Vaandering, E. W.; Vernieri, C.; Verzocchi, M.; Vidal, R.; Wang, M.; Weber, H. A.; Whitbeck, A.; Wu, W.; Acosta, D.; Avery, P.; Bortignon, P.; Bourilkov, D.; Brinkerhoff, A.; Carnes, A.; Carver, M.; Curry, D.; Field, R. D.; Furic, I. K.; Gleyzer, S. V.; Joshi, B. M.; Konigsberg, J.; Korytov, A.; Kotov, K.; Ma, P.; Matchev, K.; Mei, H.; Mitselmakher, G.; Shi, K.; Sperka, D.; Terentyev, N.; Thomas, L.; Wang, J.; Wang, S.; Yelton, J.; Joshi, Y. R.; Linn, S.; Markowitz, P.; Rodriguez, J. L.; Ackert, A.; Adams, T.; Askew, A.; Hagopian, S.; Hagopian, V.; Johnson, K. F.; Kolberg, T.; Martinez, G.; Perry, T.; Prosper, H.; Saha, A.; Santra, A.; Sharma, V.; Yohay, R.; Baarmand, M. M.; Bhopatkar, V.; Colafranceschi, S.; Hohlmann, M.; Noonan, D.; Roy, T.; Yumiceva, F.; Adams, M. R.; Apanasevich, L.; Berry, D.; Betts, R. R.; Cavanaugh, R.; Chen, X.; Dittmer, S.; Evdokimov, O.; Gerber, C. E.; Hangal, D. A.; Hofman, D. J.; Jung, K.; Kamin, J.; Sandoval Gonzalez, I. D.; Tonjes, M. B.; Varelas, N.; Wang, H.; Wang, X.; Wu, Z.; Zhang, J.; Bilki, B.; Clarida, W.; Dilsiz, K.; Durgut, S.; Gandrajula, R. P.; Haytmyradov, M.; Khristenko, V.; Merlo, J.-P.; Mermerkaya, H.; Mestvirishvili, A.; Moeller, A.; Nachtman, J.; Ogul, H.; Onel, Y.; Ozok, F.; Penzo, A.; Snyder, C.; Tiras, E.; Wetzel, J.; Yi, K.; Blumenfeld, B.; Cocoros, A.; Eminizer, N.; Fehling, D.; Feng, L.; Gritsan, A. V.; Hung, W. T.; Maksimovic, P.; Roskes, J.; Sarica, U.; Swartz, M.; Xiao, M.; You, C.; Al-bataineh, A.; Baringer, P.; Bean, A.; Benitez, J. F.; Boren, S.; Bowen, J.; Castle, J.; Khalil, S.; Kropivnitskaya, A.; Majumder, D.; Mcbrayer, W.; Murray, M.; Rogan, C.; Royon, C.; Sanders, S.; Schmitz, E.; Tapia Takaki, J. D.; Wang, Q.; Ivanov, A.; Kaadze, K.; Maravin, Y.; Modak, A.; Mohammadi, A.; Saini, L. K.; Skhirtladze, N.; Rebassoo, F.; Wright, D.; Baden, A.; Baron, O.; Belloni, A.; Eno, S. C.; Feng, Y.; Ferraioli, C.; Hadley, N. J.; Jabeen, S.; Jeng, G. Y.; Kellogg, R. G.; Kunkle, J.; Mignerey, A. C.; Ricci-Tam, F.; Shin, Y. H.; Skuja, A.; Tonwar, S. C.; Abercrombie, D.; Allen, B.; Azzolini, V.; Barbieri, R.; Baty, A.; Bauer, G.; Bi, R.; Brandt, S.; Busza, W.; Cali, I. A.; D'Alfonso, M.; Demiragli, Z.; Gomez Ceballos, G.; Goncharov, M.; Harris, P.; Hsu, D.; Hu, M.; Iiyama, Y.; Innocenti, G. M.; Klute, M.; Kovalskyi, D.; Lee, Y.-J.; Levin, A.; Luckey, P. D.; Maier, B.; Marini, A. C.; Mcginn, C.; Mironov, C.; Narayanan, S.; Niu, X.; Paus, C.; Roland, C.; Roland, G.; Stephans, G. S. F.; Sumorok, K.; Tatar, K.; Velicanu, D.; Wang, J.; Wang, T. W.; Wyslouch, B.; Zhaozhong, S.; Benvenuti, A. C.; Chatterjee, R. M.; Evans, A.; Hansen, P.; Kalafut, S.; Kubota, Y.; Lesko, Z.; Mans, J.; Nourbakhsh, S.; Ruckstuhl, N.; Rusack, R.; Turkewitz, J.; Wadud, M. A.; Acosta, J. G.; Oliveros, S.; Avdeeva, E.; Bloom, K.; Claes, D. R.; Fangmeier, C.; Golf, F.; Gonzalez Suarez, R.; Kamalieddin, R.; Kravchenko, I.; Monroy, J.; Siado, J. E.; Snow, G. R.; Stieger, B.; Godshalk, A.; Harrington, C.; Iashvili, I.; Nguyen, D.; Parker, A.; Rappoccio, S.; Roozbahani, B.; Alverson, G.; Barberis, E.; Freer, C.; Hortiangtham, A.; Massironi, A.; Morse, D. M.; Orimoto, T.; Teixeira De Lima, R.; Wamorkar, T.; Wang, B.; Wisecarver, A.; Wood, D.; Bhattacharya, S.; Charaf, O.; Hahn, K. A.; Mucia, N.; Odell, N.; Schmitt, M. H.; Sung, K.; Trovato, M.; Velasco, M.; Bucci, R.; Dev, N.; Hildreth, M.; Hurtado Anampa, K.; Jessop, C.; Karmgard, D. J.; Kellams, N.; Lannon, K.; Li, W.; Loukas, N.; Marinelli, N.; Meng, F.; Mueller, C.; Musienko, Y.; Planer, M.; Reinsvold, A.; Ruchti, R.; Siddireddy, P.; Smith, G.; Taroni, S.; Wayne, M.; Wightman, A.; Wolf, M.; Woodard, A.; Alimena, J.; Antonelli, L.; Bylsma, B.; Durkin, L. S.; Flowers, S.; Francis, B.; Hart, A.; Hill, C.; Ji, W.; Ling, T. Y.; Luo, W.; Winer, B. L.; Wulsin, H. W.; Cooperstein, S.; Driga, O.; Elmer, P.; Hardenbrook, J.; Hebda, P.; Higginbotham, S.; Kalogeropoulos, A.; Lange, D.; Luo, J.; Marlow, D.; Mei, K.; Ojalvo, I.; Olsen, J.; Palmer, C.; Piroué, P.; Salfeld-Nebgen, J.; Stickland, D.; Tully, C.; Malik, S.; Norberg, S.; Barker, A.; Barnes, V. E.; Das, S.; Gutay, L.; Jones, M.; Jung, A. W.; Khatiwada, A.; Miller, D. H.; Neumeister, N.; Peng, C. C.; Qiu, H.; Schulte, J. F.; Sun, J.; Wang, F.; Xiao, R.; Xie, W.; Cheng, T.; Dolen, J.; Parashar, N.; Chen, Z.; Ecklund, K. M.; Freed, S.; Geurts, F. J. M.; Guilbaud, M.; Kilpatrick, M.; Li, W.; Michlin, B.; Padley, B. P.; Roberts, J.; Rorie, J.; Shi, W.; Tu, Z.; Zabel, J.; Zhang, A.; Bodek, A.; de Barbaro, P.; Demina, R.; Duh, Y. t.; Ferbel, T.; Galanti, M.; Garcia-Bellido, A.; Han, J.; Hindrichs, O.; Khukhunaishvili, A.; Lo, K. H.; Tan, P.; Verzetti, M.; Ciesielski, R.; Goulianos, K.; Mesropian, C.; Agapitos, A.; Chou, J. P.; Gershtein, Y.; Gómez Espinosa, T. A.; Halkiadakis, E.; Heindl, M.; Hughes, E.; Kaplan, S.; Kunnawalkam Elayavalli, R.; Kyriacou, S.; Lath, A.; Montalvo, R.; Nash, K.; Osherson, M.; Saka, H.; Salur, S.; Schnetzer, S.; Sheffield, D.; Somalwar, S.; Stone, R.; Thomas, S.; Thomassen, P.; Walker, M.; Delannoy, A. G.; Heideman, J.; Riley, G.; Rose, K.; Spanier, S.; Thapa, K.; Bouhali, O.; Castaneda Hernandez, A.; Celik, A.; Dalchenko, M.; De Mattia, M.; Delgado, A.; Dildick, S.; Eusebi, R.; Gilmore, J.; Huang, T.; Kamon, T.; Mueller, R.; Pakhotin, Y.; Patel, R.; Perloff, A.; Perniè, L.; Rathjens, D.; Safonov, A.; Tatarinov, A.; Akchurin, N.; Damgov, J.; De Guio, F.; Dudero, P. R.; Faulkner, J.; Gurpinar, E.; Kunori, S.; Lamichhane, K.; Lee, S. W.; Mengke, T.; Muthumuni, S.; Peltola, T.; Undleeb, S.; Volobouev, I.; Wang, Z.; Greene, S.; Gurrola, A.; Janjam, R.; Johns, W.; Maguire, C.; Melo, A.; Ni, H.; Padeken, K.; Ruiz Alvarez, J. D.; Sheldon, P.; Tuo, S.; Velkovska, J.; Xu, Q.; Arenton, M. W.; Barria, P.; Cox, B.; Hirosky, R.; Joyce, M.; Ledovskoy, A.; Li, H.; Neu, C.; Sinthuprasith, T.; Wang, Y.; Wolfe, E.; Xia, F.; Harr, R.; Karchin, P. E.; Poudyal, N.; Sturdy, J.; Thapa, P.; Zaleski, S.; Brodski, M.; Buchanan, J.; Caillol, C.; Carlsmith, D.; Dasu, S.; Dodd, L.; Duric, S.; Gomber, B.; Grothe, M.; Herndon, M.; Hervé, A.; Hussain, U.; Klabbers, P.; Lanaro, A.; Levine, A.; Long, K.; Loveless, R.; Rekovic, V.; Ruggles, T.; Savin, A.; Smith, N.; Smith, W. H.; Woods, N.

2018-05-01

Modifications of the properties of jets in PbPb collisions, relative to those in pp collisions, are studied at a nucleon-nucleon center-of-mass energy of √{s_{NN}}=5.02 TeV via correlations of charged particles with the jet axis in relative pseudorapidity (Δ η), relative azimuth (Δ ϕ), and relative angular distance from the jet axis Δ r=√{(Δ η )^2+{(Δ φ )}^2} . This analysis uses data collected with the CMS detector at the LHC, corresponding to integrated luminosities of 404 μb-1 and 27.4 pb-1 for PbPb and pp collisions, respectively. Charged particle number densities, jet fragmentation functions, and jet shapes are presented as a function of PbPb collision centrality and charged-particle track transverse momentum, providing a differential description of jet modifications due to interactions with the quark-gluon plasma. [Figure not available: see fulltext.

Saturated fat supplementation interacts with dietary forage neutral detergent fiber content during the immediate postpartum and carryover periods in Holstein cows: Production responses and digestibility of nutrients.

PubMed

Piantoni, P; Lock, A L; Allen, M S

2015-05-01

Forty-eight multiparous cows were used in a randomized complete block design experiment with a 2×2 factorial arrangement of treatments to determine the interaction between a highly saturated free FA supplement (SFFA) and dietary forage neutral detergent fiber (fNDF) content on production responses and nutrient digestibility of dairy cows in the postpartum period. Treatment diets were offered from 1 to 29d postpartum (postpartum period; PP) and contained 20 or 26% fNDF (50:50 corn silage:alfalfa silage and hay, dry matter basis) and 0 or 2% SFFA [Energy Booster 100 (Milk Specialties Global, Eden Prairie, MN); 96.1% FA: 46.2% C18:0 and 37.0% C16:0]. From 30 to 71d postpartum (carryover period), a common diet (~23% fNDF, 0% SFFA) was offered to all cows to evaluate carryover effects of the treatment diets early in lactation. During the PP, higher fNDF decreased dry matter intake (DMI) by 2.0 kg/d, whereas SFFA supplementation increased it by 1.4kg/d. In addition, high fNDF with 0% SFFA decreased DMI compared with the other diets and this difference increased throughout the PP. Treatments did not affect 3.5% fat-corrected milk yield during the PP but did during the carryover period when SFFA supplementation decreased 3.5% fat-corrected milk yield for the low-fNDF diet (51.1 vs. 58.7kg/d), but not for the high-fNDF diet (58.5 vs. 58.0kg/d). During the PP, lower fNDF and SFFA supplementation decreased body condition score loss. A tendency for an interaction between fNDF and SFFA indicated that low fNDF with 2% SFFA decreased body condition score loss compared with the other diets (-0.49 vs. -0.89). During the PP, lower fNDF and 2% SFFA supplementation decreased feed efficiency (3.5% fat-corrected milk/DMI) by 0.30 and 0.23 units, respectively. The low-fNDF diet with 2% SFFA decreased feed efficiency compared with other diets early in the PP, but this difference decreased over time. Supplementation of SFFA in the PP favored energy partitioning to body reserves and limited DMI depression for the high-fNDF diet, which might allow higher-fNDF diets to be fed to cows in the PP. However, SFFA supplemented in the low-fNDF diet during the PP affected production negatively in the carryover period. Dietary fNDF and SFFA interacted, affecting performance in the PP with carryover effects when cows were fed a common diet in early lactation. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Comprehensive Analysis of Cytomegalovirus pp65 Antigen-Specific CD8+ T Cell Responses According to Human Leukocyte Antigen Class I Allotypes and Intraindividual Dominance.

PubMed

Hyun, Seung-Joo; Sohn, Hyun-Jung; Lee, Hyun-Joo; Lee, Seon-Duk; Kim, Sueon; Sohn, Dae-Hee; Hong, Cheol-Hwa; Choi, Haeyoun; Cho, Hyun-Il; Kim, Tai-Gyu

2017-01-01

To define whether individual human leukocyte antigen (HLA) class I allotypes are used preferentially in human cytomegalovirus (CMV)-specific cytotoxic T lymphocyte responses, CD8 + T cell responses restricted by up to six HLA class I allotypes in an individual were measured in parallel using K562-based artificial antigen-presenting cells expressing both CMV pp65 antigen and one of 32 HLA class I allotypes (7 HLA-A, 14 HLA-B, and 11 HLA-C) present in 50 healthy Korean donors. The CD8 + T cell responses to pp65 in the HLA-C allotypes were lower than responses to those in HLA-A and -B allotypes and there was no difference between the HLA-A and HLA-B loci. HLA-A*02:01, -B*07:02, and -C*08:01 showed the highest magnitude and frequency of immune responses to pp65 at each HLA class I locus. However, HLA-A*02:07, -B*59:01, -B*58:01, -B*15:11, -C*03:02, and -C*02:02 did not show any immune responses. Although each individual has up to six different HLA allotypes, 46% of the donors showed one allotype, 24% showed two allotypes, and 2% showed three allotypes that responded to pp65. Interestingly, the frequencies of HLA-A alleles were significantly correlated with the positivity of specific allotypes. Our results demonstrate that specific HLA class I allotypes are preferentially used in the CD8 + T cell immune response to pp65 and that a hierarchy among HLA class I allotypes is present in an individual.

The Joint US/UK 1990 Epoch world Magnetic Model

DTIC Science & Technology

1991-10-01

N cE’ "- 4 94 0 -a N fP 9u 1 I. - 4 4I opN uI uI - - - - - - -- - 9 IrI 06 ~. -A 9u. f3 0. v’ u4 -3 .0- 4 CC 00 ’C. -u -29 G- 01 W’ 10’ WCC...RE/R AR=AOR**2 C C BR=0O. BT=0O. BP=0O. BPP =O. C DO 70 N=1,MAXORD AR=AR*AOR DO 60 M=0O,N C COMPUTE UNNORMALIZED, ASSOCIATED LEGENDRE POLYNOMIALS AND...N- 1) ELSEI PP(N)=CT*PP(N I )-K(N,M)*PP(N-.2) END IF PARP=AR*PP(N) BPP = BPP +FM(M)*TEMP2*PARP ENDIF C CI 60 CONTINUE 70 CONTINUE CI C IF (ST .EQ. 0.0

Peperomia pellucida leaf extract as immunostimulator in controlling motile aeromonad septicemia due to Aeromonas hydrophila in red hybrid tilapia, Oreochromis spp. farming

PubMed Central

Lee, S. W.; Sim, K. Y.; Wendy, W.; Zulhisyam, A. K.

2016-01-01

Aim: This study was revealed the potential of Peperomia pellucida leaf extract as an immunostimulator agent in controlling motile aeromonad septicemia due to Aeromonas hydrophila in red hybrid tilapia, Oreochromis sp. Materials and Methods: In the present study, minimum inhibitory concentration (MIC) of P. pellucida leaf extract against A. hydrophila was determined through two-fold microbroth dilution method. The plant extract was screening for its active compound using a gas chromatograph mass spectrometer, and the effectiveness of P. pellucida leaf extract as an immunostimulator agent was evaluated. The experimental fish were fed with medicated feed at three different concentrations (25 mg/kg, PP-25; 50 mg/kg, PP-50; and 100 mg/kg, PP-100) of P. pellucida leaf extract for 1 week before they were intraperitoneally exposed to A. hydrophila. Enzyme-linked immunosorbent assay was carried out to determine the value of antibody response to A. hydrophila in fish from a group of fish that received medicated feed, and the percentage of total cumulative mortality of the experimental fish were observed at the end of the experiment. Results: The results showed that the major bioactive compound is phytol (40%), and the MIC value was 31.5 mg/L. The value of antibody response to A. hydrophila in fish from a group of fish which received medicated feed (PP-25, 0.128±0.014 optical density [OD]; PP-50, 0.132±0.003 OD; and PP-100, 0.171±0.02 OD) was found significantly higher (p<0.05) compared to fish did not receive medicated feed (0.00 OD). Whereas, percentage cumulative mortality of fish from all groups of fish received medicated feed (PP-25, 18.0±3.2%; PP-50, 18.2±2.8%; and PP-100, 17.7±1.8%) were found significantly lower (p<0.05) compared to a group of fish did not receive medicated feed (83.2±1.4%). Conclusion: The findings of the present study indicated the huge potential of P. pellucida leaf extract as natural immunostimulator agent for aquaculture uses. PMID:27057104

Peperomia pellucida leaf extract as immunostimulator in controlling motile aeromonad septicemia due to Aeromonas hydrophila in red hybrid tilapia, Oreochromis spp. farming.

PubMed

Lee, S W; Sim, K Y; Wendy, W; Zulhisyam, A K

2016-03-01

This study was revealed the potential of Peperomia pellucida leaf extract as an immunostimulator agent in controlling motile aeromonad septicemia due to Aeromonas hydrophila in red hybrid tilapia, Oreochromis sp. In the present study, minimum inhibitory concentration (MIC) of P. pellucida leaf extract against A. hydrophila was determined through two-fold microbroth dilution method. The plant extract was screening for its active compound using a gas chromatograph mass spectrometer, and the effectiveness of P. pellucida leaf extract as an immunostimulator agent was evaluated. The experimental fish were fed with medicated feed at three different concentrations (25 mg/kg, PP-25; 50 mg/kg, PP-50; and 100 mg/kg, PP-100) of P. pellucida leaf extract for 1 week before they were intraperitoneally exposed to A. hydrophila. Enzyme-linked immunosorbent assay was carried out to determine the value of antibody response to A. hydrophila in fish from a group of fish that received medicated feed, and the percentage of total cumulative mortality of the experimental fish were observed at the end of the experiment. The results showed that the major bioactive compound is phytol (40%), and the MIC value was 31.5 mg/L. The value of antibody response to A. hydrophila in fish from a group of fish which received medicated feed (PP-25, 0.128±0.014 optical density [OD]; PP-50, 0.132±0.003 OD; and PP-100, 0.171±0.02 OD) was found significantly higher (p<0.05) compared to fish did not receive medicated feed (0.00 OD). Whereas, percentage cumulative mortality of fish from all groups of fish received medicated feed (PP-25, 18.0±3.2%; PP-50, 18.2±2.8%; and PP-100, 17.7±1.8%) were found significantly lower (p<0.05) compared to a group of fish did not receive medicated feed (83.2±1.4%). The findings of the present study indicated the huge potential of P. pellucida leaf extract as natural immunostimulator agent for aquaculture uses.

Post-translational generation of constitutively active cores from larger phosphatases in the malaria parasite, Plasmodium falciparum: implications for proteomics

PubMed Central

Kumar, Rajinder; Musiyenko, Alla; Oldenburg, Anja; Adams, Brian; Barik, Sailen

2004-01-01

Background Although the complete genome sequences of a large number of organisms have been determined, the exact proteomes need to be characterized. More specifically, the extent to which post-translational processes such as proteolysis affect the synthesized proteins has remained unappreciated. We examined this issue in selected protein phosphatases of the protease-rich malaria parasite, Plasmodium falciparum. Results P. falciparum encodes a number of Ser/Thr protein phosphatases (PP) whose catalytic subunits are composed of a catalytic core and accessory domains essential for regulation of the catalytic activity. Two examples of such regulatory domains are found in the Ca+2-regulated phosphatases, PP7 and PP2B (calcineurin). The EF-hand domains of PP7 and the calmodulin-binding domain of PP2B are essential for stimulation of the phosphatase activity by Ca+2. We present biochemical evidence that P. falciparum generates these full-length phosphatases as well as their catalytic cores, most likely as intermediates of a proteolytic degradation pathway. While the full-length phosphatases are activated by Ca+2, the processed cores are constitutively active and either less responsive or unresponsive to Ca+2. The processing is extremely rapid, specific, and occurs in vivo. Conclusions Post-translational cleavage efficiently degrades complex full-length phosphatases in P. falciparum. In the course of such degradation, enzymatically active catalytic cores are produced as relatively stable intermediates. The universality of such proteolysis in other phosphatases or other multi-domain proteins and its potential impact on the overall proteome of a cell merits further investigation. PMID:15230980

Diversity in genomic organisation, developmental regulation and distribution of the murine PR72/B" subunits of protein phosphatase 2A

PubMed Central

Zwaenepoel, Karen; Louis, Justin V; Goris, Jozef; Janssens, Veerle

2008-01-01

Background Protein phosphatase 2A (PP2A) is a serine/threonine-specific phosphatase displaying vital functions in growth and development through its role in various signalling pathways. PP2A holoenzymes comprise a core dimer composed of a catalytic C and a structural A subunit, which can associate with a variable B-type subunit. The importance of the B-type subunits for PP2A regulation cannot be overestimated as they determine holoenzyme localisation, activity and substrate specificity. Three B-type subunit families have been identified: PR55/B, PR61/B' and PR72/B", of which the latter is currently the least characterised. Results We deduced the sequences and genomic organisation of the different murine PR72/B" isoforms: three genes encode nine isoforms, five of which are abundantly expressed and give rise to genuine PP2A subunits. Thereby, one novel subunit was identified. Using Northern blotting, we examined the tissue-specific and developmental expression of these subunits. All subunits are highly expressed in heart, suggesting an important cardiac function. Immunohistochemical analysis revealed a striated expression pattern of PR72 and PR130 in heart and skeletal muscle, but not in bladder smooth muscle. The subcellular localisation and cell cycle regulatory ability of several PR72/B" isoforms were determined, demonstrating differences as well as similarities. Conclusion In contrast to PR55/B and PR61/B', the PR72/B" family seems evolutionary more divergent, as only two of the murine genes have a human orthologue. We have integrated these results in a more consistent nomenclature of both human and murine PR72/B" genes and their transcripts/proteins. Our results provide a platform for the future generation of PR72/B" knockout mice. PMID:18715506

Drosophila Uri, a PP1α binding protein, is essential for viability, maintenance of DNA integrity and normal transcriptional activity

PubMed Central

Kirchner, Jasmin; Vissi, Emese; Gross, Sascha; Szoor, Balazs; Rudenko, Andrey; Alphey, Luke; White-Cooper, Helen

2008-01-01

Background Protein phosphatase 1 (PP1) is involved in diverse cellular processes, and is targeted to substrates via interaction with many different protein binding partners. PP1 catalytic subunits (PP1c) fall into PP1α and PP1β subfamilies based on sequence analysis, however very few PP1c binding proteins have been demonstrated to discriminate between PP1α and PP1β. Results URI (unconventional prefoldin RPB5 interactor) is a conserved molecular chaperone implicated in a variety of cellular processes, including the transcriptional response to nutrient signalling and maintenance of DNA integrity. We show that Drosophila Uri binds PP1α with much higher affinity than PP1β, and that this ability to discriminate between PP1c forms is conserved to humans. Most Uri is cytoplasmic, however we found some protein associated with active RNAPII on chromatin. We generated a uri loss of function allele, and show that uri is essential for viability in Drosophila. uri mutants have transcriptional defects, reduced cell viability and differentiation in the germline, and accumulate DNA damage in their nuclei. Conclusion Uri is the first PP1α specific binding protein to be described in Drosophila. Uri protein plays a role in transcriptional regulation. Activity of uri is required to maintain DNA integrity and cell survival in normal development. PMID:18412953

Effects of Protease, Phytase and a Bacillus sp. Direct-Fed Microbial on Nutrient and Energy Digestibility, Ileal Brush Border Digestive Enzyme Activity and Cecal Short-Chain Fatty Acid Concentration in Broiler Chickens

PubMed Central

Murugesan, Ganapathi R.; Romero, Luis F.; Persia, Michael E.

2014-01-01

Two experiments were conducted to determine the effects of protease and phytase (PP) and a Bacillus sp. direct-fed microbial (DFM) on dietary energy and nutrient utilization in broiler chickens. In the first experiment, Ross 308 broiler chicks were fed diets supplemented with PP and DFM in a 2×2 factorial arrangement. The 4 diets (control (CON), CON + PP, CON + DFM, and CON + PP + DFM) were fed from 15–21 days of age. In Experiment 1, significant interaction (P≤0.01) between PP and DFM on the apparent ileal digestibility coefficient for starch, crude protein, and amino acid indicated that both additives increased the digestibility. Both additives increased the nitrogen retention coefficient with a significant interaction (P≤0.01). Although no interaction was observed, significant main effects (P≤0.01) for nitrogen-corrected apparent ME (AMEn) for PP or DFM indicated an additive response. In a follow-up experiment, Ross 308 broiler chicks were fed the same experimental diets from 1–21 days of age. Activities of ileal brush border maltase, sucrase, and L-alanine aminopeptidase were increased (P≤0.01) by PP addition, while a trend (P = 0.07) for increased sucrase activity was observed in chickens fed DFM, in Experiment 2. The proportion of cecal butyrate was increased (P≤0.01) by DFM addition. Increased nutrient utilization and nitrogen retention appear to involve separate but complementary mechanisms for PP and DFM, however AMEn responses appear to have separate and additive mechanisms. PMID:25013936

1E7-03, a low MW compound targeting host protein phosphatase-1, inhibits HIV-1 transcription

PubMed Central

Ammosova, Tatyana; Platonov, Maxim; Ivanov, Andrei; Kont, Yasemin Saygideğer; Kumari, Namita; Kehn-Hall, Kylene; Jerebtsova, Marina; Kulkarni, Amol A; Üren, Aykut; Kovalskyy, Dmytro; Nekhai, Sergei

2014-01-01

Background and Purpose HIV-1 transcription is activated by the Tat protein which recruits the cyclin-dependent kinase CDK9/cyclin T1 to TAR RNA. Tat binds to protein phosphatase-1 (PP1) through the Q35VCF38 sequence and translocates PP1 to the nucleus. PP1 dephosphorylates CDK9 and activates HIV-1 transcription. We have synthesized a low MW compound 1H4, that targets PP1 and prevents HIV-1 Tat interaction with PP1 and inhibits HIV-1 gene transcription. Here, we report our further work with the 1H4-derived compounds and analysis of their mechanism of action. Experimental Approach Using the 1H4-PP1 complex as a model, we iteratively designed and synthesized follow-up libraries that were analysed for the inhibition of HIV-1 transcription and toxicity. We also confirmed the mechanism of action of the PP1-targeting molecules by determining the affinity of binding of these molecules to PP1, by analysing their effects on PP1 activity, disruption of PP1 binding to Tat and shuttling of PP1 to the nucleus. Key Results We identified a tetrahydroquinoline derivative, compound 7, which disrupted the interaction of Tat with PP1. We further optimized compound 7 and obtained compound 7c, renamed 1E7-03, which inhibited HIV-1 with low IC50 (fivefold lower than the previously reported compound, 1H4), showed no cytotoxicity and displayed a plasma half-life greater than 8 h in mice. 1E7-03 bound to PP1 in vitro and prevented shuttling of PP1 into the nucleus. Conclusions and Implications Our study shows that low MW compounds that functionally mimic the PP1-binding RVxF peptide can inhibit HIV-1 transcription by deregulating PP1. PMID:25073485

Measurement of the B^{±} Meson Nuclear Modification Factor in Pb-Pb Collisions at sqrt[s_{NN}]=5.02  TeV.

PubMed

Sirunyan, A M; Tumasyan, A; Adam, W; Asilar, E; Bergauer, T; Brandstetter, J; Brondolin, E; Dragicevic, M; Erö, J; Flechl, M; Friedl, M; Frühwirth, R; Ghete, V M; Hörmann, N; Hrubec, J; Jeitler, M; König, A; Krätschmer, I; Liko, D; Matsushita, T; Mikulec, I; Rabady, D; Rad, N; Rohringer, H; Schieck, J; Strauss, J; Waltenberger, W; Wulz, C-E; Chekhovsky, V; Mossolov, V; Suarez Gonzalez, J; Shumeiko, N; Alderweireldt, S; De Wolf, E A; Janssen, X; Lauwers, J; Van De Klundert, M; Van Haevermaet, H; Van Mechelen, P; Van Remortel, N; Van Spilbeeck, A; Abu Zeid, S; Blekman, F; D'Hondt, J; De Bruyn, I; De Clercq, J; Deroover, K; Lowette, S; Moortgat, S; Moreels, L; Olbrechts, A; Python, Q; Skovpen, K; Tavernier, S; Van Doninck, W; Van Mulders, P; Van Parijs, I; Brun, H; Clerbaux, B; De Lentdecker, G; Delannoy, H; Fasanella, G; Favart, L; Goldouzian, R; Grebenyuk, A; Karapostoli, G; Lenzi, T; Luetic, J; Maerschalk, T; Marinov, A; Randle-Conde, A; Seva, T; Vander Velde, C; Vanlaer, P; Vannerom, D; Yonamine, R; Zenoni, F; Zhang, F; Cimmino, A; Cornelis, T; Dobur, D; Fagot, A; Gul, M; Khvastunov, I; Poyraz, D; Salva, S; Schöfbeck, R; Tytgat, M; Van Driessche, W; Verbeke, W; Zaganidis, N; Bakhshiansohi, H; Bondu, O; Brochet, S; Bruno, G; Caudron, A; De Visscher, S; Delaere, C; Delcourt, M; Francois, B; Giammanco, A; Jafari, A; Komm, M; Krintiras, G; Lemaitre, V; Magitteri, A; Mertens, A; Musich, M; Piotrzkowski, K; Quertenmont, L; Vidal Marono, M; Wertz, S; Beliy, N; Aldá Júnior, W L; Alves, F L; Alves, G A; Brito, L; Hensel, C; Moraes, A; Pol, M E; Rebello Teles, P; Belchior Batista Das Chagas, E; Carvalho, W; Chinellato, J; Custódio, A; Da Costa, E M; Da Silveira, G G; De Jesus Damiao, D; Fonseca De Souza, S; Huertas Guativa, L M; Malbouisson, H; Mora Herrera, C; Mundim, L; Nogima, H; Santoro, A; Sznajder, A; Tonelli Manganote, E J; Torres Da Silva De Araujo, F; Vilela Pereira, A; Ahuja, S; Bernardes, C A; Fernandez Perez Tomei, T R; Gregores, E M; Mercadante, P G; Moon, C S; Novaes, S F; Padula, Sandra S; Romero Abad, D; Ruiz Vargas, J C; Aleksandrov, A; Hadjiiska, R; Iaydjiev, P; Rodozov, M; Stoykova, S; Sultanov, G; Vutova, M; Dimitrov, A; Glushkov, I; Litov, L; Pavlov, B; Petkov, P; Fang, W; Gao, X; Ahmad, M; Bian, J G; Chen, G M; Chen, H S; Chen, M; Chen, Y; Jiang, C H; Leggat, D; Liu, Z; Romeo, F; Shaheen, S M; Spiezia, A; Tao, J; Wang, C; Wang, Z; Yazgan, E; Zhang, H; Zhao, J; Ban, Y; Chen, G; Li, Q; Liu, S; Mao, Y; Qian, S J; Wang, D; Xu, Z; Avila, C; Cabrera, A; Chaparro Sierra, L F; Florez, C; González Hernández, C F; Ruiz Alvarez, J D; Godinovic, N; Lelas, D; Puljak, I; Ribeiro Cipriano, P M; Sculac, T; Antunovic, Z; Kovac, M; Brigljevic, V; Ferencek, D; Kadija, K; Mesic, B; Susa, T; Ather, M W; Attikis, A; Mavromanolakis, G; Mousa, J; Nicolaou, C; Ptochos, F; Razis, P A; Rykaczewski, H; Finger, M; Finger, M; Carrera Jarrin, E; Assran, Y; Mahmoud, M A; Mahrous, A; Dewanjee, R K; Kadastik, M; Perrini, L; Raidal, M; Tiko, A; Veelken, C; Eerola, P; Pekkanen, J; Voutilainen, M; Härkönen, J; Järvinen, T; Karimäki, V; Kinnunen, R; Lampén, T; Lassila-Perini, K; Lehti, S; Lindén, T; Luukka, P; Tuominen, E; Tuominiemi, J; Tuovinen, E; Talvitie, J; Tuuva, T; Besancon, M; Couderc, F; Dejardin, M; Denegri, D; Faure, J L; Ferri, F; Ganjour, S; Ghosh, S; Givernaud, A; Gras, P; Hamel de Monchenault, G; Jarry, P; Kucher, I; Locci, E; Machet, M; Malcles, J; Rander, J; Rosowsky, A; Sahin, M Ö; Titov, M; Abdulsalam, A; Antropov, I; Baffioni, S; Beaudette, F; Busson, P; Cadamuro, L; Chapon, E; Charlot, C; Davignon, O; Granier de Cassagnac, R; Jo, M; Lisniak, S; Lobanov, A; Miné, P; Nguyen, M; Ochando, C; Ortona, G; Paganini, P; Pigard, P; Regnard, S; Salerno, R; Sirois, Y; Stahl Leiton, A G; Strebler, T; Yilmaz, Y; Zabi, A; Agram, J-L; Andrea, J; Bloch, D; Brom, J-M; Buttignol, M; Chabert, E C; Chanon, N; Collard, C; Conte, E; Coubez, X; Fontaine, J-C; Gelé, D; Goerlach, U; Le Bihan, A-C; Van Hove, P; Gadrat, S; Beauceron, S; Bernet, C; Boudoul, G; Chierici, R; Contardo, D; Courbon, B; Depasse, P; El Mamouni, H; Fay, J; Finco, L; Gascon, S; Gouzevitch, M; Grenier, G; Ille, B; Lagarde, F; Laktineh, I B; Lethuillier, M; Mirabito, L; Pequegnot, A L; Perries, S; Popov, A; Sordini, V; Vander Donckt, M; Viret, S; Khvedelidze, A; Tsamalaidze, Z; Autermann, C; Beranek, S; Feld, L; Kiesel, M K; Klein, K; Lipinski, M; Preuten, M; Schomakers, C; Schulz, J; Verlage, T; Albert, A; Brodski, M; Dietz-Laursonn, E; Duchardt, D; Endres, M; Erdmann, M; Erdweg, S; Esch, T; Fischer, R; Güth, A; Hamer, M; Hebbeker, T; Heidemann, C; Hoepfner, K; Knutzen, S; Merschmeyer, M; Meyer, A; Millet, P; Mukherjee, S; Olschewski, M; Padeken, K; Pook, T; Radziej, M; Reithler, H; Rieger, M; Scheuch, F; Sonnenschein, L; Teyssier, D; Thüer, S; Flügge, G; Kargoll, B; Kress, T; Künsken, A; Lingemann, J; Müller, T; Nehrkorn, A; Nowack, A; Pistone, C; Pooth, O; Stahl, A; Aldaya Martin, M; Arndt, T; Asawatangtrakuldee, C; Beernaert, K; Behnke, O; Behrens, U; Bin Anuar, A A; Borras, K; Botta, V; Campbell, A; Connor, P; Contreras-Campana, C; Costanza, F; Diez Pardos, C; Eckerlin, G; Eckstein, D; Eichhorn, T; Eren, E; Gallo, E; Garay Garcia, J; Geiser, A; Gizhko, A; Grados Luyando, J M; Grohsjean, A; Gunnellini, P; Harb, A; Hauk, J; Hempel, M; Jung, H; Kalogeropoulos, A; Kasemann, M; Keaveney, J; Kleinwort, C; Korol, I; Krücker, D; Lange, W; Lelek, A; Lenz, T; Leonard, J; Lipka, K; Lohmann, W; Mankel, R; Melzer-Pellmann, I-A; Meyer, A B; Mittag, G; Mnich, J; Mussgiller, A; Ntomari, E; Pitzl, D; Placakyte, R; Raspereza, A; Roland, B; Savitskyi, M; Saxena, P; Shevchenko, R; Spannagel, S; Stefaniuk, N; Van Onsem, G P; Walsh, R; Wen, Y; Wichmann, K; Wissing, C; Bein, S; Blobel, V; Centis Vignali, M; Draeger, A R; Dreyer, T; Garutti, E; Gonzalez, D; Haller, J; Hoffmann, M; Junkes, A; Klanner, R; Kogler, R; Kovalchuk, N; Kurz, S; Lapsien, T; Marchesini, I; Marconi, D; Meyer, M; Niedziela, M; Nowatschin, D; Pantaleo, F; Peiffer, T; Perieanu, A; Scharf, C; Schleper, P; Schmidt, A; Schumann, S; Schwandt, J; Sonneveld, J; Stadie, H; Steinbrück, G; Stober, F M; Stöver, M; Tholen, H; Troendle, D; Usai, E; Vanelderen, L; Vanhoefer, A; Vormwald, B; Akbiyik, M; Barth, C; Baur, S; Baus, C; Berger, J; Butz, E; Caspart, R; Chwalek, T; Colombo, F; De Boer, W; Dierlamm, A; Freund, B; Friese, R; Giffels, M; Gilbert, A; Haitz, D; Hartmann, F; Heindl, S M; Husemann, U; Kassel, F; Kudella, S; Mildner, H; Mozer, M U; Müller, Th; Plagge, M; Quast, G; Rabbertz, K; Schröder, M; Shvetsov, I; Sieber, G; Simonis, H J; Ulrich, R; Wayand, S; Weber, M; Weiler, T; Williamson, S; Wöhrmann, C; Wolf, R; Anagnostou, G; Daskalakis, G; Geralis, T; Giakoumopoulou, V A; Kyriakis, A; Loukas, D; Topsis-Giotis, I; Kesisoglou, S; Panagiotou, A; Saoulidou, N; Evangelou, I; Flouris, G; Foudas, C; Kokkas, P; Manthos, N; Papadopoulos, I; Paradas, E; Strologas, J; Triantis, F A; Csanad, M; Filipovic, N; Pasztor, G; Bencze, G; Hajdu, C; Horvath, D; Sikler, F; Veszpremi, V; Vesztergombi, G; Zsigmond, A J; Beni, N; Czellar, S; Karancsi, J; Makovec, A; Molnar, J; Szillasi, Z; Bartók, M; Raics, P; Trocsanyi, Z L; Ujvari, B; Choudhury, S; Komaragiri, J R; Bahinipati, S; Bhowmik, S; Mal, P; Mandal, K; Nayak, A; Sahoo, D K; Sahoo, N; Swain, S K; Bansal, S; Beri, S B; Bhatnagar, V; Chawla, R; Dhingra, N; Bhawandeep, U; Kalsi, A K; Kaur, A; Kaur, M; Kumar, R; Kumari, P; Mehta, A; Mittal, M; Singh, J B; Walia, G; Kumar, Ashok; Shah, Aashaq; Bhardwaj, A; Chauhan, S; Choudhary, B C; Garg, R B; Keshri, S; Malhotra, S; Naimuddin, M; Ranjan, K; Sharma, R; Sharma, V; Bhardwaj, R; Bhattacharya, R; Bhattacharya, S; Dey, S; Dutt, S; Dutta, S; Ghosh, S; Majumdar, N; Modak, A; Mondal, K; Mukhopadhyay, S; Nandan, S; Purohit, A; Roy, A; Roy, D; Roy Chowdhury, S; Sarkar, S; Sharan, M; Thakur, S; Behera, P K; Chudasama, R; Dutta, D; Jha, V; Kumar, V; Mohanty, A K; Netrakanti, P K; Pant, L M; Shukla, P; Topkar, A; Aziz, T; Dugad, S; Mahakud, B; Mitra, S; Mohanty, G B; Parida, B; Sur, N; Sutar, B; Banerjee, S; Bhattacharya, S; Chatterjee, S; Das, P; Guchait, M; Jain, Sa; Kumar, S; Maity, M; Majumder, G; Mazumdar, K; Sarkar, T; Wickramage, N; Chauhan, S; Dube, S; Hegde, V; Kapoor, A; Kothekar, K; Pandey, S; Rane, A; Sharma, S; Chenarani, S; Eskandari Tadavani, E; Etesami, S M; Khakzad, M; Mohammadi Najafabadi, M; Naseri, M; Paktinat Mehdiabadi, S; Rezaei Hosseinabadi, F; Safarzadeh, B; Zeinali, M; Felcini, M; Grunewald, M; Abbrescia, M; Calabria, C; Caputo, C; Colaleo, A; Creanza, D; Cristella, L; De Filippis, N; De Palma, M; Fiore, L; Iaselli, G; Maggi, G; Maggi, M; Miniello, G; My, S; Nuzzo, S; Pompili, A; Pugliese, G; Radogna, R; Ranieri, A; Selvaggi, G; Sharma, A; Silvestris, L; Venditti, R; Verwilligen, P; Abbiendi, G; Battilana, C; Bonacorsi, D; Braibant-Giacomelli, S; Brigliadori, L; Campanini, R; Capiluppi, P; Castro, A; Cavallo, F R; Chhibra, S S; Cuffiani, M; Dallavalle, G M; Fabbri, F; Fanfani, A; Fasanella, D; Giacomelli, P; Guiducci, L; Marcellini, S; Masetti, G; Navarria, F L; Perrotta, A; Rossi, A M; Rovelli, T; Siroli, G P; Tosi, N; Albergo, S; Costa, S; Di Mattia, A; Giordano, F; Potenza, R; Tricomi, A; Tuve, C; Barbagli, G; Chatterjee, K; Ciulli, V; Civinini, C; D'Alessandro, R; Focardi, E; Lenzi, P; Meschini, M; Paoletti, S; Russo, L; Sguazzoni, G; Strom, D; Viliani, L; Benussi, L; Bianco, S; Fabbri, F; Piccolo, D; Primavera, F; Calvelli, V; Ferro, F; Robutti, E; Tosi, S; Brianza, L; Brivio, F; Ciriolo, V; Dinardo, M E; Fiorendi, S; Gennai, S; Ghezzi, A; Govoni, P; Malberti, M; Malvezzi, S; Manzoni, R A; Menasce, D; Moroni, L; Paganoni, M; Pauwels, K; Pedrini, D; Pigazzini, S; Ragazzi, S; Tabarelli de Fatis, T; Buontempo, S; Cavallo, N; Di Guida, S; Esposito, M; Fabozzi, F; Fienga, F; Iorio, A O M; Khan, W A; Lanza, G; Lista, L; Meola, S; Paolucci, P; Sciacca, C; Thyssen, F; Azzi, P; Bacchetta, N; Benato, L; Bisello, D; Boletti, A; Carlin, R; Carvalho Antunes De Oliveira, A; Dall'Osso, M; De Castro Manzano, P; Dorigo, T; Gasparini, F; Gasparini, U; Gozzelino, A; Lacaprara, S; Margoni, M; Meneguzzo, A T; Pantano, D; Pozzobon, N; Ronchese, P; Rossin, R; Sgaravatto, M; Simonetto, F; Torassa, E; Ventura, S; Zanetti, M; Zotto, P; Braghieri, A; Fallavollita, F; Magnani, A; Montagna, P; Ratti, S P; Re, V; Ressegotti, M; Riccardi, C; Salvini, P; Vai, I; Vitulo, P; Alunni Solestizi, L; Bilei, G M; Ciangottini, D; Fanò, L; Lariccia, P; Leonardi, R; Mantovani, G; Mariani, V; Menichelli, M; Saha, A; Santocchia, A; Spiga, D; Androsov, K; Azzurri, P; Bagliesi, G; Bernardini, J; Boccali, T; Borrello, L; Castaldi, R; Ciocci, M A; Dell'Orso, R; Fedi, G; Giassi, A; Grippo, M T; Ligabue, F; Lomtadze, T; Martini, L; Messineo, A; Palla, F; Rizzi, A; Savoy-Navarro, A; Spagnolo, P; Tenchini, R; Tonelli, G; Venturi, A; Verdini, P G; Barone, L; Cavallari, F; Cipriani, M; Del Re, D; Diemoz, M; Gelli, S; Longo, E; Margaroli, F; Marzocchi, B; Meridiani, P; Organtini, G; Paramatti, R; Preiato, F; Rahatlou, S; Rovelli, C; Santanastasio, F; Amapane, N; Arcidiacono, R; Argiro, S; Arneodo, M; Bartosik, N; Bellan, R; Biino, C; Cartiglia, N; Cenna, F; Costa, M; Covarelli, R; Degano, A; Demaria, N; Kiani, B; Mariotti, C; Maselli, S; Migliore, E; Monaco, V; Monteil, E; Monteno, M; Obertino, M M; Pacher, L; Pastrone, N; Pelliccioni, M; Pinna Angioni, G L; Ravera, F; Romero, A; Ruspa, M; Sacchi, R; Shchelina, K; Sola, V; Solano, A; Staiano, A; Traczyk, P; Belforte, S; Casarsa, M; Cossutti, F; Della Ricca, G; Zanetti, A; Kim, D H; Kim, G N; Kim, M S; Lee, J; Lee, S; Lee, S W; Oh, Y D; Sekmen, S; Son, D C; Yang, Y C; Lee, A; Kim, H; Moon, D H; Brochero Cifuentes, J A; Goh, J; Kim, T J; Cho, S; Choi, S; Go, Y; Gyun, D; Ha, S; Hong, B; Jo, Y; Kim, Y; Lee, K; Lee, K S; Lee, S; Lim, J; Park, S K; Roh, Y; Almond, J; Kim, J; Lee, H; Oh, S B; Radburn-Smith, B C; Seo, S H; Yang, U K; Yoo, H D; Yu, G B; Choi, M; Kim, H; Kim, J H; Lee, J S H; Park, I C; Ryu, G; Choi, Y; Hwang, C; Lee, J; Yu, I; Dudenas, V; Juodagalvis, A; Vaitkus, J; Ahmed, I; Ibrahim, Z A; Md Ali, M A B; Mohamad Idris, F; Wan Abdullah, W A T; Yusli, M N; Zolkapli, Z; Castilla-Valdez, H; De La Cruz-Burelo, E; Heredia-De La Cruz, I; Lopez-Fernandez, R; Mejia Guisao, J; Sanchez-Hernandez, A; Carrillo Moreno, S; Oropeza Barrera, C; Vazquez Valencia, F; Pedraza, I; Salazar Ibarguen, H A; Uribe Estrada, C; Morelos Pineda, A; Krofcheck, D; Butler, P H; Ahmad, A; Ahmad, M; Hassan, Q; Hoorani, H R; Saddique, A; Shah, M A; Shoaib, M; Waqas, M; Bialkowska, H; Bluj, M; Boimska, B; Frueboes, T; Górski, M; Kazana, M; Nawrocki, K; Romanowska-Rybinska, K; Szleper, M; Zalewski, P; Bunkowski, K; Byszuk, A; Doroba, K; Kalinowski, A; Konecki, M; Krolikowski, J; Misiura, M; Olszewski, M; Pyskir, A; Walczak, M; Bargassa, P; Beirão Da Cruz E Silva, C; Calpas, B; Di Francesco, A; Faccioli, P; Gallinaro, M; Hollar, J; Leonardo, N; Lloret Iglesias, L; Nemallapudi, M V; Seixas, J; Toldaiev, O; Vadruccio, D; Varela, J; Afanasiev, S; Bunin, P; Gavrilenko, M; Golutvin, I; Gorbunov, I; Kamenev, A; Karjavin, V; Lanev, A; Malakhov, A; Matveev, V; Palichik, V; Perelygin, V; Shmatov, S; Shulha, S; Skatchkov, N; Smirnov, V; Voytishin, N; Zarubin, A; Ivanov, Y; Kim, V; Kuznetsova, E; Levchenko, P; Murzin, V; Oreshkin, V; Smirnov, I; Sulimov, V; Uvarov, L; Vavilov, S; Vorobyev, A; Andreev, Yu; Dermenev, A; Gninenko, S; Golubev, N; Karneyeu, A; Kirsanov, M; Krasnikov, N; Pashenkov, A; Tlisov, D; Toropin, A; Epshteyn, V; Gavrilov, V; Lychkovskaya, N; Popov, V; Pozdnyakov, I; Safronov, G; Spiridonov, A; Toms, M; Vlasov, E; Zhokin, A; Aushev, T; Bylinkin, A; Chistov, R; Danilov, M; Polikarpov, S; Andreev, V; Azarkin, M; Dremin, I; Kirakosyan, M; Terkulov, A; Baskakov, A; Belyaev, A; Boos, E; Demiyanov, A; Ershov, A; Gribushin, A; Kodolova, O; Korotkikh, V; Lokhtin, I; Miagkov, I; Obraztsov, S; Petrushanko, S; Savrin, V; Snigirev, A; Vardanyan, I; Blinov, V; Skovpen, Y; Shtol, D; Azhgirey, I; Bayshev, I; Bitioukov, S; Elumakhov, D; Kachanov, V; Kalinin, A; Konstantinov, D; Krychkine, V; Petrov, V; Ryutin, R; Sobol, A; Troshin, S; Tyurin, N; Uzunian, A; Volkov, A; Adzic, P; Cirkovic, P; Devetak, D; Dordevic, M; Milosevic, J; Rekovic, V; Alcaraz Maestre, J; Barrio Luna, M; Cerrada, M; Colino, N; De La Cruz, B; Delgado Peris, A; Escalante Del Valle, A; Fernandez Bedoya, C; Fernández Ramos, J P; Flix, J; Fouz, M C; Garcia-Abia, P; Gonzalez Lopez, O; Goy Lopez, S; Hernandez, J M; Josa, M I; Pérez-Calero Yzquierdo, A; Puerta Pelayo, J; Quintario Olmeda, A; Redondo, I; Romero, L; Soares, M S; de Trocóniz, J F; Missiroli, M; Moran, D; Cuevas, J; Erice, C; Fernandez Menendez, J; Gonzalez Caballero, I; González Fernández, J R; Palencia Cortezon, E; Sanchez Cruz, S; Suárez Andrés, I; Vischia, P; Vizan Garcia, J M; Cabrillo, I J; Calderon, A; Chazin Quero, B; Curras, E; Fernandez, M; Garcia-Ferrero, J; Gomez, G; Lopez Virto, A; Marco, J; Martinez Rivero, C; Matorras, F; Piedra Gomez, J; Rodrigo, T; Ruiz-Jimeno, A; Scodellaro, L; Trevisani, N; Vila, I; Vilar Cortabitarte, R; Abbaneo, D; Auffray, E; Baillon, P; Ball, A H; Barney, D; Bianco, M; Bloch, P; Bocci, A; Botta, C; Camporesi, T; Castello, R; Cepeda, M; Cerminara, G; Chen, Y; d'Enterria, D; Dabrowski, A; Daponte, V; David, A; De Gruttola, M; De Roeck, A; Di Marco, E; Dobson, M; Dorney, B; du Pree, T; Dünser, M; Dupont, N; Elliott-Peisert, A; Everaerts, P; Franzoni, G; Fulcher, J; Funk, W; Gigi, D; Gill, K; Glege, F; Gulhan, D; Gundacker, S; Guthoff, M; Harris, P; Hegeman, J; Innocente, V; Janot, P; Karacheban, O; Kieseler, J; Kirschenmann, H; Knünz, V; Kornmayer, A; Kortelainen, M J; Lange, C; Lecoq, P; Lourenço, C; Lucchini, M T; Malgeri, L; Mannelli, M; Martelli, A; Meijers, F; Merlin, J A; Mersi, S; Meschi, E; Milenovic, P; Moortgat, F; Mulders, M; Neugebauer, H; Orfanelli, S; Orsini, L; Pape, L; Perez, E; Peruzzi, M; Petrilli, A; Petrucciani, G; Pfeiffer, A; Pierini, M; Racz, A; Reis, T; Rolandi, G; Rovere, M; Sakulin, H; Sauvan, J B; Schäfer, C; Schwick, C; Seidel, M; Sharma, A; Silva, P; Sphicas, P; Steggemann, J; Stoye, M; Tosi, M; Treille, D; Triossi, A; Tsirou, A; Veckalns, V; Veres, G I; Verweij, M; Wardle, N; Zagozdzinska, A; Zeuner, W D; Bertl, W; Deiters, K; Erdmann, W; Horisberger, R; Ingram, Q; Kaestli, H C; Kotlinski, D; Langenegger, U; Rohe, T; Wiederkehr, S A; Bachmair, F; Bäni, L; Berger, P; Bianchini, L; Casal, B; Dissertori, G; Dittmar, M; Donegà, M; Grab, C; Heidegger, C; Hits, D; Hoss, J; Kasieczka, G; Klijnsma, T; Lustermann, W; Mangano, B; Marionneau, M; Martinez Ruiz Del Arbol, P; Masciovecchio, M; Meinhard, M T; Meister, D; Micheli, F; Musella, P; Nessi-Tedaldi, F; Pandolfi, F; Pata, J; Pauss, F; Perrin, G; Perrozzi, L; Quittnat, M; Rossini, M; Schönenberger, M; Starodumov, A; Tavolaro, V R; Theofilatos, K; Vesterbacka Olsson, M L; Wallny, R; Zhu, D H; Aarrestad, T K; Amsler, C; Caminada, L; Canelli, M F; De Cosa, A; Donato, S; Galloni, C; Hinzmann, A; Hreus, T; Kilminster, B; Ngadiuba, J; Pinna, D; Rauco, G; Robmann, P; Salerno, D; Seitz, C; Yang, Y; Zucchetta, A; Candelise, V; Doan, T H; Jain, Sh; Khurana, R; Konyushikhin, M; Kuo, C M; Lin, W; Pozdnyakov, A; Yu, S S; Kumar, Arun; Chang, P; Chang, Y H; Chao, Y; Chen, K F; Chen, P H; Fiori, F; Hou, W-S; Hsiung, Y; Liu, Y F; Lu, R-S; Miñano Moya, M; Paganis, E; Psallidas, A; Tsai, J F; Asavapibhop, B; Kovitanggoon, K; Singh, G; Srimanobhas, N; Adiguzel, A; Boran, F; Damarseckin, S; Demiroglu, Z S; Dozen, C; Eskut, E; Girgis, S; Gokbulut, G; Guler, Y; Hos, I; Kangal, E E; Kara, O; Kayis Topaksu, A; Kiminsu, U; Oglakci, M; Onengut, G; Ozdemir, K; Ozturk, S; Polatoz, A; Tali, B; Turkcapar, S; Zorbakir, I S; Zorbilmez, C; Bilin, B; Karapinar, G; Ocalan, K; Yalvac, M; Zeyrek, M; Gülmez, E; Kaya, M; Kaya, O; Yetkin, E A; Cakir, A; Cankocak, K; Grynyov, B; Levchuk, L; Sorokin, P; Aggleton, R; Ball, F; Beck, L; Brooke, J J; Burns, D; Clement, E; Cussans, D; Flacher, H; Goldstein, J; Grimes, M; Heath, G P; Heath, H F; Jacob, J; Kreczko, L; Lucas, C; Newbold, D M; Paramesvaran, S; Poll, A; Sakuma, T; Seif El Nasr-Storey, S; Smith, D; Smith, V J; Belyaev, A; Brew, C; Brown, R M; Calligaris, L; Cieri, D; Cockerill, D J A; Coughlan, J A; Harder, K; Harper, S; Olaiya, E; Petyt, D; Shepherd-Themistocleous, C H; Thea, A; Tomalin, I R; Williams, T; Baber, M; Bainbridge, R; Buchmuller, O; Bundock, A; Casasso, S; Citron, M; Colling, D; Corpe, L; Dauncey, P; Davies, G; De Wit, A; Della Negra, M; Di Maria, R; Dunne, P; Elwood, A; Futyan, D; Haddad, Y; Hall, G; Iles, G; James, T; Lane, R; Laner, C; Lyons, L; Magnan, A-M; Malik, S; Mastrolorenzo, L; Nash, J; Nikitenko, A; Pela, J; Pesaresi, M; Raymond, D M; Richards, A; Rose, A; Scott, E; Seez, C; Summers, S; Tapper, A; Uchida, K; Vazquez Acosta, M; Virdee, T; Wright, J; Zenz, S C; Cole, J E; Hobson, P R; Khan, A; Kyberd, P; Reid, I D; Symonds, P; Teodorescu, L; Turner, M; Borzou, A; Call, K; Dittmann, J; Hatakeyama, K; Liu, H; Pastika, N; Bartek, R; Dominguez, A; Buccilli, A; Cooper, S I; Henderson, C; Rumerio, P; West, C; Arcaro, D; Avetisyan, A; Bose, T; Gastler, D; Rankin, D; Richardson, C; Rohlf, J; Sulak, L; Zou, D; Benelli, G; Cutts, D; Garabedian, A; Hakala, J; Heintz, U; Hogan, J M; Kwok, K H M; Laird, E; Landsberg, G; Mao, Z; Narain, M; Piperov, S; Sagir, S; Spencer, E; Syarif, R; Band, R; Brainerd, C; Burns, D; Calderon De La Barca Sanchez, M; Chertok, M; Conway, J; Conway, R; Cox, P T; Erbacher, R; Flores, C; Funk, G; Gardner, M; Ko, W; Lander, R; Mclean, C; Mulhearn, M; Pellett, D; Pilot, J; Shalhout, S; Shi, M; Smith, J; Squires, M; Stolp, D; Tos, K; Tripathi, M; Wang, Z; Bachtis, M; Bravo, C; Cousins, R; Dasgupta, A; Florent, A; Hauser, J; Ignatenko, M; Mccoll, N; Saltzberg, D; Schnaible, C; Valuev, V; Bouvier, E; Burt, K; Clare, R; Ellison, J; Gary, J W; Ghiasi Shirazi, S M A; Hanson, G; Heilman, J; Jandir, P; Kennedy, E; Lacroix, F; Long, O R; Olmedo Negrete, M; Paneva, M I; Shrinivas, A; Si, W; Wei, H; Wimpenny, S; Yates, B R; Branson, J G; Cerati, G B; Cittolin, S; Derdzinski, M; Holzner, A; Klein, D; Kole, G; Krutelyov, V; Letts, J; Macneill, I; Olivito, D; Padhi, S; Pieri, M; Sani, M; Sharma, V; Simon, S; Tadel, M; Vartak, A; Wasserbaech, S; Würthwein, F; Yagil, A; Zevi Della Porta, G; Amin, N; Bhandari, R; Bradmiller-Feld, J; Campagnari, C; Dishaw, A; Dutta, V; Franco Sevilla, M; George, C; Golf, F; Gouskos, L; Gran, J; Heller, R; Incandela, J; Mullin, S D; Ovcharova, A; Qu, H; Richman, J; Stuart, D; Suarez, I; Yoo, J; Anderson, D; Bendavid, J; Bornheim, A; Lawhorn, J M; Newman, H B; Pena, C; Spiropulu, M; Vlimant, J R; Xie, S; Zhu, R Y; Andrews, M B; Ferguson, T; Paulini, M; Russ, J; Sun, M; Vogel, H; Vorobiev, I; Weinberg, M; Cumalat, J P; Ford, W T; Jensen, F; Johnson, A; Krohn, M; Leontsinis, S; Mulholland, T; Stenson, K; Wagner, S R; Alexander, J; Chaves, J; Chu, J; Dittmer, S; Mcdermott, K; Mirman, N; Patterson, J R; Rinkevicius, A; Ryd, A; Skinnari, L; Soffi, L; Tan, S M; Tao, Z; Thom, J; Tucker, J; Wittich, P; Zientek, M; Winn, D; Abdullin, S; Albrow, M; Apollinari, G; Apresyan, A; Apyan, A; Banerjee, S; Bauerdick, L A T; Beretvas, A; Berryhill, J; Bhat, P C; Bolla, G; Burkett, K; Butler, J N; Canepa, A; Cheung, H W K; Chlebana, F; Cremonesi, M; Duarte, J; Elvira, V D; Fisk, I; Freeman, J; Gecse, Z; Gottschalk, E; Gray, L; Green, D; Grünendahl, S; Gutsche, O; Harris, R M; Hasegawa, S; Hirschauer, J; Hu, Z; Jayatilaka, B; Jindariani, S; Johnson, M; Joshi, U; Klima, B; Kreis, B; Lammel, S; Lincoln, D; Lipton, R; Liu, M; Liu, T; Lopes De Sá, R; Lykken, J; Maeshima, K; Magini, N; Marraffino, J M; Maruyama, S; Mason, D; McBride, P; Merkel, P; Mrenna, S; Nahn, S; O'Dell, V; Pedro, K; Prokofyev, O; Rakness, G; Ristori, L; Schneider, B; Sexton-Kennedy, E; Soha, A; Spalding, W J; Spiegel, L; Stoynev, S; Strait, J; Strobbe, N; Taylor, L; Tkaczyk, S; Tran, N V; Uplegger, L; Vaandering, E W; Vernieri, C; Verzocchi, M; Vidal, R; Wang, M; Weber, H A; Whitbeck, A; Acosta, D; Avery, P; Bortignon, P; Brinkerhoff, A; Carnes, A; Carver, M; Curry, D; Das, S; Field, R D; Furic, I K; Konigsberg, J; Korytov, A; Kotov, K; Ma, P; Matchev, K; Mei, H; Mitselmakher, G; Rank, D; Shchutska, L; Sperka, D; Terentyev, N; Thomas, L; Wang, J; Wang, S; Yelton, J; Linn, S; Markowitz, P; Martinez, G; Rodriguez, J L; Ackert, A; Adams, T; Askew, A; Hagopian, S; Hagopian, V; Johnson, K F; Kolberg, T; Perry, T; Prosper, H; Santra, A; Yohay, R; Baarmand, M M; Bhopatkar, V; Colafranceschi, S; Hohlmann, M; Noonan, D; Roy, T; Yumiceva, F; Adams, M R; Apanasevich, L; Berry, D; Betts, R R; Cavanaugh, R; Chen, X; Evdokimov, O; Gerber, C E; Hangal, D A; Hofman, D J; Jung, K; Kamin, J; Sandoval Gonzalez, I D; Tonjes, M B; Trauger, H; Varelas, N; Wang, H; Wu, Z; Zhang, J; Bilki, B; Clarida, W; Dilsiz, K; Durgut, S; Gandrajula, R P; Haytmyradov, M; Khristenko, V; Merlo, J-P; Mermerkaya, H; Mestvirishvili, A; Moeller, A; Nachtman, J; Ogul, H; Onel, Y; Ozok, F; Penzo, A; Snyder, C; Tiras, E; Wetzel, J; Yi, K; Blumenfeld, B; Cocoros, A; Eminizer, N; Fehling, D; Feng, L; Gritsan, A V; Maksimovic, P; Roskes, J; Sarica, U; Swartz, M; Xiao, M; You, C; Al-Bataineh, A; Baringer, P; Bean, A; Boren, S; Bowen, J; Castle, J; Khalil, S; Kropivnitskaya, A; Majumder, D; Mcbrayer, W; Murray, M; Royon, C; Sanders, S; Stringer, R; Tapia Takaki, J D; Wang, Q; Ivanov, A; Kaadze, K; Maravin, Y; Mohammadi, A; Saini, L K; Skhirtladze, N; Toda, S; Rebassoo, F; Wright, D; Anelli, C; Baden, A; Baron, O; Belloni, A; Calvert, B; Eno, S C; Ferraioli, C; Hadley, N J; Jabeen, S; Jeng, G Y; Kellogg, R G; Kunkle, J; Mignerey, A C; Ricci-Tam, F; Shin, Y H; Skuja, A; Tonwar, S C; Abercrombie, D; Allen, B; Azzolini, V; Barbieri, R; Baty, A; Bi, R; Bierwagen, K; Brandt, S; Busza, W; Cali, I A; D'Alfonso, M; Demiragli, Z; Gomez Ceballos, G; Goncharov, M; Hsu, D; Iiyama, Y; Innocenti, G M; Klute, M; Kovalskyi, D; Lai, Y S; Lee, Y-J; Levin, A; Luckey, P D; Maier, B; Marini, A C; Mcginn, C; Mironov, C; Narayanan, S; Niu, X; Paus, C; Roland, C; Roland, G; Salfeld-Nebgen, J; Stephans, G S F; Tatar, K; Turner, A; Velicanu, D; Wang, J; Wang, T W; Wyslouch, B; Benvenuti, A C; Chatterjee, R M; Evans, A; Hansen, P; Kalafut, S; Kao, S C; Kubota, Y; Lesko, Z; Mans, J; Nourbakhsh, S; Ruckstuhl, N; Rusack, R; Tambe, N; Turkewitz, J; Acosta, J G; Oliveros, S; Avdeeva, E; Bloom, K; Claes, D R; Fangmeier, C; Gonzalez Suarez, R; Kamalieddin, R; Kravchenko, I; Monroy, J; Siado, J E; Snow, G R; Stieger, B; Alyari, M; Dolen, J; Godshalk, A; Harrington, C; Iashvili, I; Kharchilava, A; Parker, A; Rappoccio, S; Roozbahani, B; Alverson, G; Barberis, E; Hortiangtham, A; Massironi, A; Morse, D M; Nash, D; Orimoto, T; Teixeira De Lima, R; Trocino, D; Wang, R-J; Wood, D; Bhattacharya, S; Charaf, O; Hahn, K A; Mucia, N; Odell, N; Pollack, B; Schmitt, M H; Sung, K; Trovato, M; Velasco, M; Dev, N; Hildreth, M; Hurtado Anampa, K; Jessop, C; Karmgard, D J; Kellams, N; Lannon, K; Loukas, N; Marinelli, N; Meng, F; Mueller, C; Musienko, Y; Planer, M; Reinsvold, A; Ruchti, R; Rupprecht, N; Smith, G; Taroni, S; Wayne, M; Wolf, M; Woodard, A; Alimena, J; Antonelli, L; Bylsma, B; Durkin, L S; Flowers, S; Francis, B; Hart, A; Hill, C; Ji, W; Liu, B; Luo, W; Puigh, D; Winer, B L; Wulsin, H W; Benaglia, A; Cooperstein, S; Driga, O; Elmer, P; Hardenbrook, J; Hebda, P; Lange, D; Luo, J; Marlow, D; Mei, K; Ojalvo, I; Olsen, J; Palmer, C; Piroué, P; Stickland, D; Svyatkovskiy, A; Tully, C; Malik, S; Norberg, S; Barker, A; Barnes, V E; Folgueras, S; Gutay, L; Jha, M K; Jones, M; Jung, A W; Khatiwada, A; Miller, D H; Neumeister, N; Schulte, J F; Sun, J; Wang, F; Xie, W; Cheng, T; Parashar, N; Stupak, J; Adair, A; Akgun, B; Chen, Z; Ecklund, K M; Geurts, F J M; Guilbaud, M; Li, W; Michlin, B; Northup, M; Padley, B P; Roberts, J; Rorie, J; Tu, Z; Zabel, J; Betchart, B; Bodek, A; de Barbaro, P; Demina, R; Duh, Y T; Ferbel, T; Galanti, M; Garcia-Bellido, A; Han, J; Hindrichs, O; Khukhunaishvili, A; Lo, K H; Tan, P; Verzetti, M; Ciesielski, R; Goulianos, K; Mesropian, C; Agapitos, A; Chou, J P; Gershtein, Y; Gómez Espinosa, T A; Halkiadakis, E; Heindl, M; Hughes, E; Kaplan, S; Kunnawalkam Elayavalli, R; Kyriacou, S; Lath, A; Montalvo, R; Nash, K; Osherson, M; Saka, H; Salur, S; Schnetzer, S; Sheffield, D; Somalwar, S; Stone, R; Thomas, S; Thomassen, P; Walker, M; Foerster, M; Heideman, J; Riley, G; Rose, K; Spanier, S; Thapa, K; Bouhali, O; Castaneda Hernandez, A; Celik, A; Dalchenko, M; De Mattia, M; Delgado, A; Dildick, S; Eusebi, R; Gilmore, J; Huang, T; Kamon, T; Mueller, R; Pakhotin, Y; Patel, R; Perloff, A; Perniè, L; Rathjens, D; Safonov, A; Tatarinov, A; Ulmer, K A; Akchurin, N; Damgov, J; De Guio, F; Dragoiu, C; Dudero, P R; Faulkner, J; Gurpinar, E; Kunori, S; Lamichhane, K; Lee, S W; Libeiro, T; Peltola, T; Undleeb, S; Volobouev, I; Wang, Z; Greene, S; Gurrola, A; Janjam, R; Johns, W; Maguire, C; Melo, A; Ni, H; Sheldon, P; Tuo, S; Velkovska, J; Xu, Q; Arenton, M W; Barria, P; Cox, B; Hirosky, R; Ledovskoy, A; Li, H; Neu, C; Sinthuprasith, T; Sun, X; Wang, Y; Wolfe, E; Xia, F; Clarke, C; Harr, R; Karchin, P E; Sturdy, J; Zaleski, S; Belknap, D A; Buchanan, J; Caillol, C; Dasu, S; Dodd, L; Duric, S; Gomber, B; Grothe, M; Herndon, M; Hervé, A; Hussain, U; Klabbers, P; Lanaro, A; Levine, A; Long, K; Loveless, R; Pierro, G A; Polese, G; Ruggles, T; Savin, A; Smith, N; Smith, W H; Taylor, D; Woods, N

2017-10-13

The differential production cross sections of B^{±} mesons are measured via the exclusive decay channels B^{±}→J/ψK^{±}→μ^{+}μ^{-}K^{±} as a function of transverse momentum in pp and Pb-Pb collisions at a center-of-mass energy sqrt[s_{NN}]=5.02  TeV per nucleon pair with the CMS detector at the LHC. The pp(Pb-Pb) data set used for this analysis corresponds to an integrated luminosity of 28.0  pb^{-1} (351  μb^{-1}). The measurement is performed in the B^{±} meson transverse momentum range of 7 to 50  GeV/c, in the rapidity interval |y|<2.4. In this kinematic range, a strong suppression of the production cross section by about a factor of 2 is observed in the Pb-Pb system in comparison to the expectation from pp reference data. These results are found to be roughly compatible with theoretical calculations incorporating beauty quark diffusion and energy loss in a quark-gluon plasma.

Amino acid supplementation of calf milk replacers containing plasma protein.

PubMed

Morrison, S Y; Campbell, J M; Drackley, J K

2017-06-01

We determined the effects of calf milk replacers containing 0, 5, or 10% bovine plasma protein (PP), either without or with the supplemental amino acids (AA) Ile and Thr, on growth and health of male Holstein calves (n = 104) for 56 d. Milk replacers were formulated to contain 22% crude protein (CP), 20% fat, and 2.0% Lys. Milk replacers (12.5% solids) were fed at a rate of 1.5% of body weight (BW) on a dry matter basis during wk 1 and 1.75% of BW beginning on d 8. Starter was introduced on d 36 so that effects of PP and AA balance in milk replacers could be isolated. Intake, respiratory scores, and fecal scores were measured daily. Body weight and stature were measured weekly and blood serum samples were obtained during wk 4. Treatments had no effects on intakes of dry matter, CP, or metabolizable energy. During wk 6 and 8, BW was less as PP inclusion increased without AA supplementation compared with the other treatments. In wk 7, calves fed the higher level of PP without AA had lower BW than calves fed either the lower level of PP without supplemented AA or the higher inclusion of PP with supplemented AA. Average daily gain and gain:feed were lowest for calves fed the higher inclusion of PP without supplemented AA; heart girth in wk 7 was smallest for those calves. During the first 21 d, occurrence of scours was greater in calves fed the control milk replacer than in calves fed milk replacers containing the higher inclusion of PP either without or with supplemental AA. Occurrence of scours was also greater for the lower inclusion of PP compared with the higher inclusion of PP when AA were supplemented. Throughout the 56-d experiment, the chance of antibiotic treatment was greater for calves fed the control milk replacer than for all other treatments except the higher inclusion of PP without supplemental AA. Additionally, chance of antibiotic treatment was greater for the higher inclusion of PP without supplemental AA than for other milk replacers with PP. Calves fed treatments with the higher inclusion of PP had fewer days of scours than the controls. All milk replacers with PP, except the milk replacer containing higher PP without supplemental AA, had fewer days of treatment with antibiotics compared to the all-milk control. Inclusion of PP provided similar performance and improved health as long as milk replacers were balanced for Ile and Thr. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The two-step electrochemical oxidation of alcohols using a novel recombinant PQQ alcohol dehydrogenase as a catalyst for a bioanode.

PubMed

Takeda, Kouta; Matsumura, Hirotoshi; Ishida, Takuya; Samejima, Masahiro; Igarashi, Kiyohiko; Nakamura, Nobuhumi; Ohno, Hiroyuki

2013-12-01

A bioanode has been developed based on the oxidation of ethanol by the recombinant pyrroloquinoline quinone (PQQ) dependent alcohol dehydrogenase from Pseudomonas putidaKT2440 heterologously expressed in Pichia pastoris. The apo form of the recombinant protein (PpADH) was purified and displayed catalytic activity for binding PQQ in the presence of Ca(2+). PpADH exhibited broad substrate specificity towards various alcohols and aldehydes. The Km values for the aldehydes of PpADH were increased compared to those for the alcohols, whereas the kcat values were unaltered. For instance, the Km values at T=298.15K (25 °C) for ethanol and acetaldehyde were 0.21 (± 0.02)mM and 5.8 (± 0.60)mM, respectively. The kcat values for ethanol and acetaldehyde were 24.8 (± 1.2) s(-1) and 31.1 (± 1.2) s(-1), respectively. The aminoferrocene was used as an electron transfer mediator between PpADH and the electrode during electrochemical experiments. The catalytic currents for the oxidation of alcohol and acetaldehyde by PpADH were also observed in this system. The electric charge for the oxidation of ethanol (Q = 2.09 × 10(-3) · C) was increased two-fold compared to that for the oxidation of acetaldehyde (Q = 0.95 × 10(-3) · C), as determined by chronoamperometric measurements. Thus, we have electrochemically demonstrated the two-step oxidation of ethanol to acetate using only PpADH. © 2013.

The Persian Gulf and the National Interest.

DTIC Science & Technology

1982-02-01

with Unique Solution,v 20 pp., Jun 1970, 234-253) AD A055 536 AD A038 535 PP 223 PP 213 "angel, Marc, "S1tochastic Mechanics of MlulolOf Mlouldl Mengel ...Theory," 54 pp.. Jun 1978. AD A058 540 PP 216 - Clasified PP 229 Mengel , Marc, "Diffusion Theory 04 Asection Rates. li pp 219 Formulation and Elnstein...CEtisetion." 60 pp., Ap 78, AD A054 422 PP 230 PP 220 Mengel . Marc, "Diffusion The"r of Reaction Rate. 11 Mowrer, Donald E., "Diegonalfaction by amop Mtrices

Dormancy-associated MADS-box genes and microRNAs jointly control dormancy transition in pear (Pyrus pyrifolia white pear group) flower bud

PubMed Central

Niu, Qingfeng; Li, Jianzhao; Cai, Danying; Qian, Minjie; Jia, Huimin; Bai, Songling; Hussain, Sayed; Liu, Guoqin; Teng, Yuanwen; Zheng, Xiaoyan

2016-01-01

Bud dormancy in perennial plants is indispensable to survival over winter and to regrowth and development in the following year. However, the molecular pathways of endo-dormancy induction, maintenance, and release are still unclear, especially in fruit crops. To identify genes with roles in regulating endo-dormancy, 30 MIKCC-type MADS-box genes were identified in the pear genome and characterized. The 30 genes were analysed to determine their phylogenetic relationships with homologous genes, genome locations, gene structure, tissue-specific transcript profiles, and transcriptional patterns during flower bud dormancy in ‘Suli’ pear (Pyrus pyrifolia white pear group). The roles in regulating bud dormancy varied among the MIKC gene family members. Yeast one-hybrid and transient assays showed that PpCBF enhanced PpDAM1 and PpDAM3 transcriptional activity during the induction of dormancy, probably by binding to the C-repeat/DRE binding site, while DAM proteins inhibited the transcriptional activity of PpFT2 during dormancy release. In the small RNA-seq analysis, 185 conserved, 24 less-conserved, and 32 pear-specific miRNAs with distinct expression patterns during bud dormancy were identified. Joint analyses of miRNAs and MIKC genes together with degradome data showed that miR6390 targeted PpDAM transcripts and degraded them to release PpFT2. Our data show that cross-talk among PpCBF, PpDAM, PpFT2, and miR6390 played important roles in regulating endo-dormancy. A model for the molecular mechanism of dormancy transition is proposed: short-term chilling in autumn activates the accumulation of CBF, which directly promotes DAM expression; DAM subsequently inhibits FT expression to induce endo-dormancy, and miR6390 degrades DAM genes to release endo-dormancy. PMID:26466664

CBe5Hn((n-4)) (n = 2-5): Hydrogen-Stabilized CBe5 Pentagons Containing Planar or Quasi-Planar Pentacoordinate Carbons.

PubMed

Guo, Jin-Chang; Ren, Guang-Ming; Miao, Chang-Qing; Tian, Wen-Juan; Wu, Yan-Bo; Wang, Xiaotai

2015-12-31

The diagonal relationship between beryllium and aluminum and the isoelectronic relationship between BeH unit and Al atom were utilized to design a new series ppC- or quasi-ppC-containing species C5v CBe5H5(+), Cs CBe5H4, C2v CBe5H3(-), and C2v CBe5H2(2-) by replacing the Al atoms in previously reported global minima planar pentacoordinate carbon (ppC) species D5h CAl5(+), C2v CAl4Be, C2v CAl3Be2(-), and C2v CAl2Be3(2-) with BeH units. The three-center two-electron (3c-2e) bonds formed between Be and bridging H atoms were crucial for the stabilization of these ppC species. The natural bond orbital (NBO) and adaptive natural density partitioning (AdNDP) analyses revealed that the central ppCs or quasi-ppCs possess the stable eight electron-shell structures. The AdNDP analyses also disclosed that these species are all 6σ+2π double-aromatic in nature. The aromaticity was proved by the calculated negative nucleus-independent chemical shifts (NICS) values. DFT and high-level CCSD(T) calculations revealed that these ppC- or quasi-ppC species are the global minimum or competitive low-lying local minimum (Cs CBe5H4) on their potential energy surfaces. The Born-Oppenheimer molecular dynamic (BOMD) simulations revealed that the H atoms in C2v CBe5H3(-) and C2v CBe5H2(2-) can easily rotate around the CBe5 cores and the structure of quasi-planar C5v CBe5H5(+) will become the planar structure at room temperature; however, these interesting dynamic behaviors did not indicate the kinetic instability as the basic ppC structures were maintained during the simulations. Therefore, it would be potentially possible to realize these interesting ppC- or quasi-ppc-species in future experiments.

The melt-recrystallization behavior of highly oriented α-iPP fibers embedded in a HIPS matrix.

PubMed

Ye, Liwei; Li, Huihui; Qiu, Zhaobin; Yan, Shouke

2015-03-21

The melt-recrystallization behavior of α-iPP fibers embedded in an amorphous HIPS matrix has been studied by means of optical microscopy. The amorphous HIPS serving as a supporter of iPP fibers does not become involved in the nucleation and crystallization process of the molten highly oriented iPP fibers. It also does not provide any birefringence under the optical microscope with crossed polarizers. This enables the study of orientation-induced β-iPP crystallization through a control of the melting status of the fibers. Through melting the fibers at different temperatures above 175 °C and subsequent recrystallization, some β-iPP crystals were always produced. The content of the β-iPP crystal depends strongly on the melting temperature and melting time of the iPP fibers. It was confirmed that melting the iPP fibers at relatively lower temperature, e.g. 176 °C, less amount of β-iPP crystals were observed. The content of β-iPP crystal enhances first with increasing melting temperature and then decreases with further increase of the fiber melting temperature. The β-iPP crystallization is found to be most favorable upon melting the fibers at 178 °C for 2 min. This demonstrates the requirement of a certain chain or chain segment orientation for generating β-iPP crystallization on the one hand, while higher orientation of the iPP chains or chain segments encourages the growth of iPP crystals in the α-form on the other hand. This has been further confirmed by varying the melting time of the fiber at different temperatures, since relaxation of the iPP molecular chains at a fixed temperature is time dependent. Moreover, the complete transformation of α-iPP fibers in some local places into β-iPP crystals implies that the αβ-transition may not be required for the orientation-induced β-iPP crystallization.

Characterizing the Hercules Thick Disk Cloud

DTIC Science & Technology

2009-01-01

merger. Key Words: Astronomy , Hercules Thick Disk Cloud, Galaxy, Star Count, Color, Photometric Parallax 2 Contents Chapter 1... Astronomy : Structure and Kinematics, 2nd ed., New York: W. H. Freeman and Company, 1981, pp 4. 5 Henbest, Guide, pp 10. 6 Mihalas, Galactic, pp 209...studies of astronomy later in his life, he focused on binary star systems and concluded that not all stars have the same absolute magnitude, thus

Gardenia jasminoides Encodes an Inhibitor-2 Protein for Protein Phosphatase Type 1

NASA Astrophysics Data System (ADS)

Gao, Lan; Li, Hao-Ming

2017-08-01

Protein phosphatase-1 (PP1) regulates diverse, essential cellular processes such as cell cycle progression, protein synthesis, muscle contraction, carbohydrate metabolism, transcription and neuronal signaling. Inhibitor-2 (I-2) can inhibit the activity of PP1 and has been found in diverse organisms. In this work, a Gardenia jasminoides fruit cDNA library was constructed, and the GjI-2 cDNA was isolated from the cDNA library by sequencing method. The GjI-2 cDNA contains a predicted 543 bp open reading frame that encodes 180 amino acids. The bioinformatics analysis suggested that the GjI-2 has conserved PP1c binding motif, and contains a conserved phosphorylation site, which is important in regulation of its activity. The three-dimensional model structure of GjI-2 was buite, its similar with the structure of I-2 from mouse. The results suggest that GjI-2 has relatively conserved RVxF, FxxR/KxR/K and HYNE motif, and these motifs are involved in interaction with PP1.

Ionic liquids as electrolytes for non-aqueous solutions electrochemical supercapacitors in a temperature range of 20 °C-80 °C

NASA Astrophysics Data System (ADS)

Zhang, Lei; Tsay, Ken; Bock, Christina; Zhang, Jiujun

2016-08-01

To increase the operating temperature of the supercapacitors (SCs) without compromising their high cycle-life, several typical fluoro- and non-fluoro containing ionic liquids (EMI-mesylate, EMI-hydrogen sulfate, PP13-triflate, PP13-TFSI, and EMI-TFSI, as shown in Fig. 1) are studied as the electrolytes to prepare organic solutions for SC performance measurements using a two-electrode cell. Both cyclic voltammograms and charge/discharge curves at various temperatures such as 20, 40, 60 and 80 °C are collected. At 60 °C, the increased performance order in both rating and cyclability measurements are found to be as follows: 1) EMI-hydrogen sulfate < PP13-TFSI < EMI-mesylate < PP13-triflate < EMI-TFSI for rating; and 2) EMI-hydrogen sulfate < EMI-mesylate < PP13-Triflate < PP13-TFSI < EMI-TFSI for life-time. The fluoro-containing group of ILs, i.e., PP13-Triflate, PP13-TFSI and EMI-TFSI can give a specific capacitance between 100 and 170 F/g for various scan rates for a conventional carbon electrode, and an extended lifetime test of 10, 000 cycles with a capacitance degradation of less than 10%, indicating that these two ion liquids can be used for SC electrolytes operated at high temperature.

Making Home Sweet and Sturdy: Toxoplasma gondii ppGalNAc-Ts Glycosylate in Hierarchical Order and Confer Cyst Wall Rigidity.

PubMed

Tomita, Tadakimi; Sugi, Tatsuki; Yakubu, Rama; Tu, Vincent; Ma, Yanfen; Weiss, Louis M

2017-01-10

The protozoan intracellular parasite Toxoplasma gondii forms latent cysts in the central nervous system (CNS) and persists for the lifetime of the host. This cyst is cloaked with a glycosylated structure called the cyst wall. Previously, we demonstrated that a mucin-like glycoprotein, CST1, localizes to the cyst wall and confers structural rigidity on brain cysts in a mucin-like domain-dependent manner. The mucin-like domain of CST1 is composed of 20 units of threonine-rich tandem repeats that are O-GalNAc glycosylated. A family of enzymes termed polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-Ts) initiates O-GalNAc glycosylation. To identify which isoforms of ppGalNAc-Ts are responsible for the glycosylation of the CST1 mucin-like domain and to evaluate the function of each ppGalNAc-T in the overall glycosylation of the cyst wall, all five ppGalNAc-T isoforms were deleted individually from the T. gondii genome. The ppGalNAc-T2 and -T3 deletion mutants produced various glycosylation defects on the cyst wall, implying that many cyst wall glycoproteins are glycosylated by T2 and T3. Both T2 and T3 glycosylate the CST1 mucin-like domain, and this glycosylation is necessary for CST1 to confer structural rigidity on the cyst wall. We established that T2 is required for the initial glycosylation of the mucin-like domain and that T3 is responsible for the sequential glycosylation on neighboring acceptor sites, demonstrating hierarchical glycosylation by two distinct initiating and filling-in ppGalNAc-Ts in an intact organism. Toxoplasma gondii is an obligate intracellular parasite that infects a third of the world's population. It can cause severe congenital disease and devastating encephalitis in immunocompromised individuals. We identified two glycosyltransferases, ppGalNAc-T2 and -T3, which are responsible for glycosylating cyst wall proteins in a hierarchical fashion. This glycosylation confers structural rigidity on the brain cyst. Our studies provide new insights into the mechanisms of O-GalNAc glycosylation in T. gondii. Copyright © 2017 Tomita et al.

Effect of dinucleoside pyrophosphates on the oligomerization of activated mononucleotides on Na(+)-montmorillonite: reaction of 5'-phosphoro-4-(dimethylamino)pyridinium [4-(CH3)2NpypA] with A5'ppA

NASA Technical Reports Server (NTRS)

Prabahar, K. J.; Ferris, J. P.

1997-01-01

The oligomerization of adenosine 5'-phosphoro-4-(dimethylamino)pyridinium (4-(CH3)2-NpypA) and diadenosine 5',5'-pyrophosphate (A5'ppA) (9:1) on Na(+)-montmorillonite was studied. The oligomers were isolated and analyzed by selective enzymatic hydrolyses and the oligomeric composition and the percent of 3',5'-phosphodiester linkages present in each fraction was determined. The longest oligomers formed (11-mers) are slightly shorter than those produced in the absence of A5'ppA (12-mers). Smaller amounts of A5'ppA are incorporated into the oligomers than in the ImpA/A5'ppA reaction. The regioselectivity of 3',5'-phosphodiester bond formation is comparable to that of the oligomerization of 4-(CH3)2NpypA alone. An explanation of these data is proposed and the possible effect of dinucleoside pyrophosphate on prebiotic RNA formation is discussed.

Two Bistable Switches Govern M Phase Entry.

PubMed

Mochida, Satoru; Rata, Scott; Hino, Hirotsugu; Nagai, Takeharu; Novák, Béla

2016-12-19

The abrupt and irreversible transition from interphase to M phase is essential to separate DNA replication from chromosome segregation. This transition requires the switch-like phosphorylation of hundreds of proteins by the cyclin-dependent kinase 1 (Cdk1):cyclin B (CycB) complex. Previous studies have ascribed these switch-like phosphorylations to the auto-activation of Cdk1:CycB through the removal of inhibitory phosphorylations on Cdk1-Tyr15 [1, 2]. The positive feedback in Cdk1 activation creates a bistable switch that makes mitotic commitment irreversible [2-4]. Here, we surprisingly find that Cdk1 auto-activation is dispensable for irreversible, switch-like mitotic entry due to a second mechanism, whereby Cdk1:CycB inhibits its counteracting phosphatase (PP2A:B55). We show that the PP2A:B55-inhibiting Greatwall (Gwl)-endosulfine (ENSA) pathway is both necessary and sufficient for switch-like phosphorylations of mitotic substrates. Using purified components of the Gwl-ENSA pathway in a reconstituted system, we found a sharp Cdk1 threshold for phosphorylation of a luminescent mitotic substrate. The Cdk1 threshold to induce mitotic phosphorylation is distinctly higher than the Cdk1 threshold required to maintain these phosphorylations-evidence for bistability. A combination of mathematical modeling and biochemical reconstitution show that the bistable behavior of the Gwl-ENSA pathway emerges from its mutual antagonism with PP2A:B55. Our results demonstrate that two interlinked bistable mechanisms provide a robust solution for irreversible and switch-like mitotic entry. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prehospital shock index and pulse pressure/heart rate ratio to predict massive transfusion after severe trauma: Retrospective analysis of a large regional trauma database.

PubMed

Pottecher, Julien; Ageron, François-Xavier; Fauché, Clémence; Chemla, Denis; Noll, Eric; Duranteau, Jacques; Chapiteau, Laurent; Payen, Jean-François; Bouzat, Pierre

2016-10-01

Early and accurate detection of severe hemorrhage is critical for a timely trigger of massive transfusion (MT). Hemodynamic indices combining heart rate (HR) and either systolic (shock index [SI]) or pulse pressure (PP) (PP/HR ratio) have been shown to track blood loss during hemorrhage. The present study assessed the accuracy of prehospital SI and PP/HR ratio to predict subsequent MT, using the gray-zone approach. This was a retrospective analysis (January 1, 2009, to December 31, 2011) of a prospectively developed trauma registry (TRENAU), in which the triage scheme combines patient severity and hospital facilities. Thresholds for MT were defined as either classic (≥10 red blood cell units within the first 24 hours [MT1]) or critical (≥3 red blood cells within the first hour [MT2]). The receiver operating characteristic curves and gray zones were defined for SI and PP/HR ratio to predict MT1 and MT2 and faced with initial triage scheme. The TRENAU registry included 3,689 trauma patients, of which 2,557 had complete chart recovery and 176 (6.9%) required MT. In the whole population, PP/HR ratio and SI moderately and similarly predicted MT1 (area under the receiver operating characteristic curve, 0.77 [95% confidence interval {CI}, 0.70-0.84] and 0.80 [95% CI, 0.74-0.87], respectively, p = 0.064) and MT2 (0.71 [95% CI, 0.67-0.76] and 0.72 [95% CI, 0.68-0.77], respectively, p = 0.48). The proportions of patients in the gray zone for PP/HR ratio and SI were 61% versus 40%, respectively, to predict MT1 (p < 0.001) and 62% versus 71%, respectively, to predict MT2 (p < 0.001). In the least severe patient, both indices had fair accuracy to predict MT1 (0.91 [95% CI, 0.82-1.00] vs. 0.87 [95% CI, 0.79-1.00]; p = 0.638), and PP/HR ratio outperformed SI to predict MT2 (0.72 [95% CI, 0.59-0.84] vs. 0.54 [95% CI, 0.33-0.74]; p < 0.015). In an unselected trauma population, prehospital SI and PP/HR ratio were moderately accurate in predicting MT. In the seemingly least severe patients, an improvement of prehospital undertriage for MT may be gained by using the PP/HR ratio. Epidemiolgic study, level III.

Is liver perfusion CT reproducible? A study on intra- and interobserver agreement of normal hepatic haemodynamic parameters obtained with two different software packages.

PubMed

Bretas, Elisa Almeida Sathler; Torres, Ulysses S; Torres, Lucas Rios; Bekhor, Daniel; Saito Filho, Celso Fernando; Racy, Douglas Jorge; Faggioni, Lorenzo; D'Ippolito, Giuseppe

2017-10-01

To evaluate the agreement between the measurements of perfusion CT parameters in normal livers by using two different software packages. This retrospective study was based on 78 liver perfusion CT examinations acquired for detecting suspected liver metastasis. Patients with any morphological or functional hepatic abnormalities were excluded. The final analysis included 37 patients (59.7 ± 14.9 y). Two readers (1 and 2) independently measured perfusion parameters using different software packages from two major manufacturers (A and B). Arterial perfusion (AP) and portal perfusion (PP) were determined using the dual-input vascular one-compartmental model. Inter-reader agreement for each package and intrareader agreement between both packages were assessed with intraclass correlation coefficients (ICC) and Bland-Altman statistics. Inter-reader agreement was substantial for AP using software A (ICC = 0.82) and B (ICC = 0.85-0.86), fair for PP using software A (ICC = 0.44) and fair to moderate for PP using software B (ICC = 0.56-0.77). Intrareader agreement between software A and B ranged from slight to moderate (ICC = 0.32-0.62) for readers 1 and 2 considering the AP parameters, and from fair to moderate (ICC = 0.40-0.69) for readers 1 and 2 considering the PP parameters. At best there was only moderate agreement between both software packages, resulting in some uncertainty and suboptimal reproducibility. Advances in knowledge: Software-dependent factors may contribute to variance in perfusion measurements, demanding further technical improvements. AP measurements seem to be the most reproducible parameter to be adopted when evaluating liver perfusion CT.

Nitrous oxide for pneumoperitoneum: no laughing matter this! A prospective single blind case controlled study.

PubMed

Rammohan, Ashwin; Manimaran, A B; Manohar, R R; Naidu, R M

2011-01-01

The search for the perfect insufflating gas has been elusive. Even though Carbon dioxide (CO(2)) is the most commonly used gas, it has numerous cardiovascular, respiratory and hemodynamic side effects, which have often been taken for granted. In the current scenario of ever expanding and complex indications for Laparoscopic Surgery these changes have an increasing implication of placing the patient at risk. Nitrous Oxide (N(2)O) has now made a comeback and shown by recent studies to be as safe as CO(2) for creating pneumoperitoneum (PP). The purpose of our study is to determine whether benefits of N(2)O (PP) outweigh those of CO(2) PP in Laparoscopic Surgery. All patients undergoing Laparoscopic Surgery over an 8 week period were divided into two groups. Data were collected prospectively for Group I {N(2)O(n = 38)} and Group II {CO(2) PP(n = 39)}. Heart rate, Mean Arterial Blood Pressure, End-Tidal CO(2), Arterial pH, Peak Airway Pressure, Minute Ventilation and O(2) Saturation were recorded before PP, 15 minutes after PP and 10 minutes after exsufflation. Intraoperative anesthetic agent and postoperative pain medication use was recorded. Pain was assessed by means of visual analog scale (VAS) at postoperative hours 2 and 4 and on day 1. Results tabulated and analyzed statistically. There was no statistical difference in age, sex, weight, complexity of surgery (type of procedure and duration of PP), Anesthetic risk, and duration of hospitalization between the two groups. Mean End-Tidal CO(2) increase was greater despite a greater mean intraoperative increase in Minute Ventilation in group II, Heart Rate, Arterial pH, Mean Arterial Pressure under anesthesia were significantly higher in group II. The quantum of intraoperative anesthetic agent and postoperative pain (as assessed by Visual Analog Scale) was less in group I. This is an initial study assessing the use of N(2)O for insufflation; the results of our study suggest N(2)O PP has a definitive advantage over CO(2) PP. Further multicentric randomized trials are necessary before N(2)O becomes the standard insufflating agent. Copyright © 2010 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Podoplanin-positive Cancer-associated Stromal Fibroblasts in Primary Tumor and Synchronous Lymph Node Metastases of HER2-overexpressing Breast Carcinomas.

PubMed

Niemiec, Joanna; Adamczyk, Agnieszka; Harazin-Lechowska, Agnieszka; Ambicka, Aleksandra; Grela-Wojewoda, Aleksandra; Majchrzyk, Kaja; Kruczak, Anna; Sas-Korczyńska, Beata; Ryś, Janusz

2018-04-01

We compared the status of stromal podoplanin-positive cancer-associated fibroblasts (ppCAFs) between primary tumors and paired synchronous lymph node metastases (LNMs) and analyzed the prognostic significance of tumoral ppCAFs in 203 patients with human epidermal growth factor receptor 2-positive breast carcinoma. ppCAFs were found in 167/203 and in 35/87 tumors and LNM, respectively. ppCAFs were most frequently found in tumors and corresponding LNM (n=52, 59.8%; p=0.001). However, for all LNMs (n=12) without ppCAFs, their paired tumors also lacked ppCAFs. In both tumors and LNMs, ppCAFs were α-smooth muscle actin-positive and cluster of differentiation 21 protein-negative, suggesting them not to be resident lymph node cells. Moreover, in our series, the presence of ppCAFs in tumors was borderline related to poor disease-free survival (p=0.058). These results speak in favor of a hypothesis suggesting ppCAFs accompany metastatic cancer cells migrating from tumor to LNMs. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Analytical method development and validation of simultaneous estimation of rabeprazole, pantoprazole, and itopride by reverse-phase high-performance liquid chromatography.

PubMed

Perumal, Senthamil Selvan; Ekambaram, Sanmuga Priya; Raja, Samundeswari

2014-12-01

A simple, selective, rapid, and precise reverse-phase high-performance liquid chromatography (RP-HPLC) method for the simultaneous estimation of rabeprazole (RP), pantoprazole (PP), and itopride (IP) has been developed. The compounds were well separated on a Phenomenex C 18 (Luna) column (250 mm × 4.6 mm, dp = 5 μm) with C 18 guard column (4 mm × 3 mm × 5 μm) with a mobile phase consisting of buffer containing 10 mM potassium dihydrogen orthophosphate (adjusted to pH 6.8): acetonitrile (70:30 v/v) at a flow rate of 1.0 mL/min and ultraviolet detection at 288 nm. The retention time of RP, PP, and IP were 5.35, 7.92, and 11.16 minutes, respectively. Validation of the proposed method was carried out according to International Conference on Harmonisation (ICH) guidelines. Linearity range was obtained for RP, PP, and IP over the concentration range of 2.5-25, 1-30, and 3-35 μg/mL and the r 2 values were 0.994, 0.978, and 0.991, respectively. The calculated limit of detection (LOD) values were 1, 0.3, and 1 μg/mL and limit of quantitation (LOQ) values were 2.5, 1, and 3 μg/mL for RP, PP, and IP correspondingly. Thus, the current study showed that the developed reverse-phase liquid chromatography method is sensitive and selective for the estimation of RP, PP, and IP in combined dosage form. Copyright © 2014. Published by Elsevier B.V.

Books Noted

NASA Astrophysics Data System (ADS)

Walsh, Edward J.

1999-09-01

Atmospheric Chemistry and Global Change Guy P. Brasseur, John J. Orlando, and Geoffrey S. Tyndall, Eds. Oxford University Press: New York, 1999. xviii + 654 pp. ISBN 0-19-510521-4. 70.00. Advances in Supramolecular Chemistry, Vol. 5 George W. Gokel, Ed. JAI Press: Stamford, CT, 1999. ix + 654 pp. ISBN 1-7623-0447-2. 109.50. Advances in Cycloaddition, Vol. 5 Michael Harmata, Ed. JAI Press: Stamford, CT, 1999. ix + 172 pp. ISBN 0-7623-0346-8. 109.50. Characterization of Powders and Aerosols Brian H. Kaye. Wiley-VCH: New York, 1999. xi + 312 pp. ISBN 3-527-28853-8. 205.00. Chemometrics M. Otto. Wiley-VCH: New York, 1999. xvi + 314 pp. ISBN 3-527-29628-x. 69.95. Flow Measurement Methods and Applications Jim E. Hardy, Jim O. Hylton, Tim E. McKnight, C. J. Remenyik, and Frances R. Ruppel. Wiley-Interscience: New York, 1999. ix + 254 pp. ISBN 0-471-24509-7. 79.95. Tailored Polymeric Materials for Controlled Delivery Systems Iain McCulloch and Shalaby W. Shalaby, Eds. ACS Symposium Series 709. Oxford University Press: New York, 1998. xi + 324 pp. ISBN 0-8412-3585-6. 115.00. Chemistry, 7th Edition Karen C. Timberlake. Addison Wesley Longman: Menlo Park, CA, 1999. xxviii + 740 pp. ISBN 0-321-03767-7. 72.19. General Chemistry, 2nd Edition John W. Hill and Ralph H. Petrucci. Prentice Hall: Upper Saddle River, NJ. 1999. xxvi + 1088 pp + appendix and index. ISBN 0-13-010318-7. $97.00.

Measurement of the resonance parameters of the chi(1)(1**3P(1)) and chi(2)(1**3P(2)) states of charmonium formed in antiproton-proton annihilations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andreotti, M.; Bagnasco, S.; Baldini, W.

2005-03-01

The authors have studied the {sup 3}P{sub J} ({chi}{sub e}) states of charmonium in formation by antiproton-proton annihilations in experiment E835 at the Fermilab Antiproton Source. The authors report new measurements of the mass, width, and B({chi}{sub cJ} {yields} {bar p}p) x {Lambda}({chi}{sub eJ} {yields} J/{psi} + anything) for the {chi}{sub c1} and {chi}{sub c2} by means of the inclusive reaction {bar p}p {yields} {chi}{sub cJ} {yields} J/{psi} + anything {yields} (e{sup +}e{sup -}) + anything. Using the subsample of events where {chi}{sub cJ} {yields} {gamma} + J/{psi} {yields} {gamma} + (e{sup +}e{sup -}) is fully reconstructed, we derive B({chi}{submore » cJ} {yields} {bar p}p) x {Lambda}({chi}{sub cJ} {yields} J/{psi} + {gamma}). They summarize the results of the E760 (updated) and E835 measurements of mass, width and B({chi}{sub cJ} {yields} {bar p}p){Lambda}({chi}{sub cJ} {yields} J/{psi} + {gamma}) (J = 0,1,2) and discuss the significance of these measurements.« less

Leaf patch clamp pressure probe measurements on olive leaves in a nearly turgorless state.

PubMed

Ehrenberger, W; Rüger, S; Rodríguez-Domínguez, C M; Díaz-Espejo, A; Fernández, J E; Moreno, J; Zimmermann, D; Sukhorukov, V L; Zimmermann, U

2012-07-01

The non-invasive leaf patch clamp pressure (LPCP) probe measures the attenuated pressure of a leaf patch, P(p) , in response to an externally applied magnetic force. P(p) is inversely coupled with leaf turgor pressure, P(c) , i.e. at high P(c) values the P(p) values are small and at low P(c) values the P(p) values are high. This relationship between P(c) and P(p) could also be verified for 2-m tall olive trees under laboratory conditions using the cell turgor pressure probe. When the laboratory plants were subjected to severe water stress (P(c) dropped below ca. 50 kPa), P(p) curves show reverse diurnal changes, i.e. during the light regime (high transpiration) a minimum P(p) value, and during darkness a peak P(p) value is recorded. This reversal of the P(p) curves was completely reversible. Upon watering, the original diurnal P(p) changes were re-established within 2-3 days. Olive trees in the field showed a similar turnover of the shape of the P(p) curves upon drought, despite pronounced fluctuations in microclimate. The reversal of the P(p) curves is most likely due to accumulation of air in the leaves. This assumption was supported with cross-sections through leaves subjected to prolonged drought. In contrast to well-watered leaves, microscopic inspection of leaves exhibiting inverse diurnal P(p) curves revealed large air-filled areas in parenchyma tissue. Significantly larger amounts of air could also be extracted from water-stressed leaves than from well-watered leaves using the cell turgor pressure probe. Furthermore, theoretical analysis of the experimental P(p) curves shows that the propagation of pressure through the nearly turgorless leaf must be exclusively dictated by air. Equations are derived that provide valuable information about the water status of olive leaves close to zero P(c) . © 2012 German Botanical Society and The Royal Botanical Society of the Netherlands.

Urinary tract infection after voiding cystourethrogram.

PubMed

Johnson, E K; Malhotra, N R; Shannon, R; Jacobson, D L; Green, J; Rigsby, C K; Holl, J L; Cheng, E Y

2017-08-01

Reported rates of post-procedural urinary tract infection (ppUTI) after voiding cystourethrogram (VCUG) are highly variable (0-42%). This study aimed to determine the risk of ppUTI after cystogram, and evaluate predictors of ppUTI. A retrospective cohort study of children undergoing VCUG or radionuclide cystogram (henceforth 'cystogram') was conducted. Children with neurogenic bladder who underwent cystogram in the operating room and without follow-up at the study institution were excluded. Incidence of symptomatic ppUTI within 7 days after cystogram was recorded. Predictors of ppUTI were evaluated using univariate statistics. A total of 1108 children (54% female, median age 1.1 years) underwent 1203 cystograms: 51% were on periprocedural antibiotics, 75% had a pre-existing urologic diagnosis (i.e., vesicoureteral reflux (VUR) or hydronephrosis; not UTI alone), and 18% had a clinical UTI within 30 days before cystogram. Of the cystograms, 41% had an abnormal cystogram and findings included VUR (82%), ureterocele (6%), and diverticula (6%). Twelve children had a ppUTI (1.0%; four girls, five uncircumcised boys, three circumcised boys; median age 0.9 years). Factors significantly associated with diagnosis of a ppUTI (Summary fig.) included: pre-existing urologic diagnosis prior to cystogram (12/12, 100% of patients with ppUTI), abnormal cystogram results (11/12, 92%), and use of periprocedural antibiotics (11/12, 92%). All 11 children with an abnormal cystogram had VUR ≥ Grade III. However, among all children with VUR ≥ Grade III, 4% (11/254) had a ppUTI. This is the largest study to date that has examined incidence and risk factors for ppUTI after cystogram. The retrospective nature of the study limited capture of some clinical details. This study demonstrated that the risk of ppUTI after a cystogram is very low (1.0% in this cohort). Having a pre-existing urologic diagnosis such as VUR or hydronephrosis was associated with ppUTI; therefore, children with moderate or high-grade VUR on cystogram may be at highest risk. Development of ppUTI after cystogram also highlighted the potential for a delay in diagnosis or oversight of a healthcare-associated infection due to several factors: 1) cystograms may be ordered, performed/interpreted, and followed up by multiple different providers; and 2) such infections are not captured by traditional healthcare-associated infection surveillance strategies. The risk of ppUTI after a cystogram is very low. Only children with pre-existing urologic diagnoses developed ppUTI in this study. This study's findings suggest that children undergoing a cystogram should not be given peri-procedural antibiotic prophylaxis for the sole purpose of ppUTI prevention. Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

The Distinction of Amyloid-β Protein Precursor (AβPP) Ratio in Platelet Between Alzheimer's Disease Patients and Controls: A Systematic Review and Meta-Analysis.

PubMed

Shi, Yachen; Gu, Lihua; Alsharif, Abdul Azeez; Zhang, Zhijun

2017-01-01

To systematically assess the clinical significance of platelet amyloid-β protein precursor (AβPP) ratio between Alzheimer's disease (AD) patients and controls. 14 articles were selected in this analysis by search of databases including PubMed and Web of Science up to December 2016. Random effects models were used to calculate the standardized mean difference (SMD). Subgroup analyses were used to detect the cause of heterogeneity. The result showed a significant drop in platelet AβPP ratio in AD patients compared to controls [SMD: -1.871; 95% CI: (-2.33, -1.41); p < 0.001; I2 = 88.0% ]. Subgroup analysis revealed races or the quality of studies may be the cause of high heterogeneity. This meta-analysis concluded that there is a close association between platelet AβPP ratio and AD. It is necessary to design a sizable sample study to further support that platelet AβPP ratio can be a biomarker of AD.

Involvement of GSK3 and PP2A in ginsenoside Rb1's attenuation of aluminum-induced tau hyperphosphorylation.

PubMed

Zhao, Hai-hua; Di, Jing; Liu, Wen-su; Liu, Hui-li; Lai, Hong; Lü, Yong-li

2013-03-15

Environmental agent aluminum, a well-known neurotoxin, has been proposed to play a role in the development of Alzheimer's disease (AD), and produced clinical and pathological features which were strikingly similar to those seen in AD brain, such as neurofibrillary tangles. Ginsenoside Rb1, highly abundant active component of ginseng, has been demonstrated to be neuroprotective against various neurotoxins. In this study we investigated the effect of Rb1 on aluminum-induced tau hyperphosphorylation in ICR mice. Mice were exposed to aluminum chloride (200 mg/kg/day) for 6 months followed by a post treatment of Rb1 (20 mg/kg/day) for another 4 months. Aluminum exposure induced the cognitive ability by Morris water maze, and upregulated the tau phosphorylation level at Ser396 accompanied by increasing p-GSK and decreasing PP2A level in motor, sensory cortex and hippocampal formation. Post treatment of Rb1 significantly improved the learning and memory and reduced the tau phosphorylation by reversing the p-GSK3 and PP2A level. Our results indicate that ginsenoside Rb1 protected mice against Al-induced toxicity. The possible mechanism may be its role in preventing tau hyperphosphorylation by regulating p-GSK3 and PP2A level, which implicate Rb1 as the potential preventive drug candidate for AD and other tau pathology-related neuronal degenerative diseases. Copyright © 2013. Published by Elsevier B.V.

Threshold value of home pulse pressure predicting arterial stiffness in patients with type 2 diabetes: KAMOGAWA-HBP study.

PubMed

Kitagawa, Noriyuki; Ushigome, Emi; Matsumoto, Shinobu; Oyabu, Chikako; Ushigome, Hidetaka; Yokota, Isao; Asano, Mai; Tanaka, Muhei; Yamazaki, Masahiro; Fukui, Michiaki

2018-03-01

This cross-sectional multicenter study was designed to evaluate the threshold value of home pulse pressure (PP) and home systolic blood pressure (SBP) predicting the arterial stiffness in 876 patients with type 2 diabetes. We measured the area under the receiver-operating characteristic curve (AUC) and estimated the ability of home PP to identify arterial stiffness using Youden-Index defined cut-off point. The arterial stiffness was measured using the brachial-ankle pulse wave velocity (baPWV). AUC for arterial stiffness in morning PP was significantly greater than that in morning SBP (P < .001). AUC for arterial stiffness in evening PP was also significantly greater than that in evening SBP (P < .001). The optimal cut-off points for morning PP and evening PP, which predicted arterial stiffness, were 54.6 and 56.9 mm Hg, respectively. Our findings indicate that we should pay more attention to increased home PP in patients with type 2 diabetes. ©2018 Wiley Periodicals, Inc.

Enhanced Induction of T Cell Immunity Using Dendritic Cells Pulsed with HIV Tat and HCMV-pp65 Fusion Protein In Vitro

PubMed Central

Park, Jung-Sun; Park, Soo-Young; Cho, Hyun-Il; Sohn, Hyun-Jung

2011-01-01

Background Cytotoxic T lymphocytes (CTLs) appear to play an important role in the control and prevention of human cytomegalovirus (HCMV) infection. The pp65 antigen is a structural protein, which has been defined as a potential target for effective immunity against HCMV infection. Incorporation of an 11 amino acid region of the HIV TAT protein transduction domain (Tat) into protein facilitates rapid, efficient entry into cells. Methods To establish a strategy for the generation of HCMV-specific CTLs in vitro, recombinant truncated N- and C-terminal pp65 protein (pp65 N&C) and N- and C-terminal pp65 protein fused with Tat (Tat/pp65 N&C) was produced in E.coli system. Peripheral blood mononuclear cells were stimulated with dendritic cells (DCs) pulsed with pp65 N&C or Tat/pp65 N&C protein and immune responses induced was examined using IFN-γ ELISPOT assay, cytotoxicity assay and tetramer staining. Results DCs pulsed with Tat/pp65N&C protein could induce higher T-cell responses in vitro compared with pp65N&C. Moreover, the DCs pulsed with Tat/pp65 N&C could stimulate both of CD8+ and CD4+ T-cell responses. The T cells induced by DCs pulsed with Tat/pp65 N&C showed higher cytotoxicity than that of pp65-pulsed DCs against autologous lymphoblastoid B-cell line (LCL) expressing the HCMV-pp65 antigen. Conclusion Our results suggest that DCs pulsed with Tat/pp65 N&C protein effectively induced pp65-specific CTL in vitro. Tat fusion recombinant protein may be useful for the development of adoptive T-cell immunotherapy and DC-based vaccines. PMID:21860612

Role of MRI T2-DRIVE in the assessment of pituitary stalk abnormalities without gadolinium in pituitary diseases.

PubMed

Godano, Elisabetta; Morana, Giovanni; Di Iorgi, Natascia; Pistorio, Angela; Allegri, Anna Elsa Maria; Napoli, Flavia; Gastaldi, Roberto; Calcagno, Annalisa; Patti, Giuseppa; Gallizia, Annalisa; Notarnicola, Sara; Giaccardi, Marta; Noli, Serena; Severino, Mariasavina; Tortora, Domenico; Rossi, Andrea; Maghnie, Mohamad

2018-06-01

To investigate the role of T2-DRIVE MRI sequence in the accurate measurement of pituitary stalk (PS) size and the identification of PS abnormalities in patients with hypothalamic-pituitary disorders without the use of gadolinium. This was a retrospective study conducted on 242 patients who underwent MRI due to pituitary dysfunction between 2006 and 2015. Among 135 eligible patients, 102 showed eutopic posterior pituitary (PP) gland and 33 showed 'ectopic' PP (EPP). Two readers independently measured the size of PS in patients with eutopic PP at the proximal, midpoint and distal levels on pre- and post-contrast T1-weighted as well as T2-DRIVE images; PS visibility was assessed on pre-contrast T1 and T2-DRIVE sequences in those with EPP. The length, height, width and volume of the anterior pituitary (AP), PP height and length and PP area were analyzed. Significant agreement between the two readers was obtained for T2-DRIVE PS measurements in patients with 'eutopic' PP; a significant difference was demonstrated between the intraclass correlation coefficient calculated on the T2-DRIVE and the T1-pre- and post-contrast sequences. The percentage of PS identified by T2-DRIVE in EPP patients was 72.7% compared to 30.3% of T1 pre-contrast sequences. A significant association was found between the visibility of PS on T2-DRIVE and the height of AP. T2-DRIVE sequence is extremely precise and reliable for the evaluation of PS size and the recognition of PS abnormalities; the use of gadolinium-based contrast media does not add significant information and may thus be avoided. © 2018 European Society of Endocrinology.

Can Authoritative Studies Be Trusted

DTIC Science & Technology

1982-07-01

Unlderwater High PP. 37 Sensitivity Zheronkov Detector: SeA Urchin ." 20 PP_* nger, a E., "The Outlook for Military Operations Aug 1963 Research,* 14 pp.. Apr...PROFESSIONAL PAPERS - 1978 TO PRESENT* PP 211 PP 222 Mlzrahi, Maurice M., "On Approximating the Circular Coverage Mizrani, Maurice M., "Correspondence Rules...Nov 1919 Limit Cycles," 19 Do., mar 1979 (Publisnea in SIAM J. Appi. (Delivered at the International Symposlun on the Sea . Math., Vol. 38, No. 2, Fog

Efficacy and safety of lumacaftor/ivacaftor combination therapy in patients with cystic fibrosis homozygous for Phe508del CFTR by pulmonary function subgroup: a pooled analysis.

PubMed

Elborn, J Stuart; Ramsey, Bonnie W; Boyle, Michael P; Konstan, Michael W; Huang, Xiaohong; Marigowda, Gautham; Waltz, David; Wainwright, Claire E

2016-08-01

Lumacaftor/ivacaftor combination therapy has shown clinical benefits in patients with cystic fibrosis homozygous for the Phe508del CFTR mutation; however, pretreatment lung function is a confounding factor that potentially affects the efficacy and safety of this therapy. We aimed to assess the efficacy and safety of lumacaftor/ivacaftor therapy in these patients, defined by specific categories of lung function. Both trials (TRAFFIC and TRANSPORT) included in this pooled analysis were multinational, randomised, double-blind, placebo-controlled, parallel-group, phase 3 studies. Eligible patients from 187 participating centres in North America, Australia, and the European Union (both trials) were aged 12 years or older with a confirmed diagnosis of cystic fibrosis, homozygous for the Phe508del CFTR mutation, and with a percent predicted FEV1 (ppFEV1) of 40-90 at the time of screening. Patients were randomly assigned with an interactive web response system (1:1:1) to receive placebo, lumacaftor (600 mg once daily) plus ivacaftor (250 mg every 12 h), or lumacaftor (400 mg every 12 h) plus ivacaftor (250 mg every 12 h) for 24 weeks. Prespecified subgroup analyses of pooled efficacy and safety data by lung function, as measured by ppFEV1, were done for patients with baseline ppFEV1 (<40 and ≥40) and screening ppFEV1 (<70 and ≥70). The primary endpoint was the absolute change from baseline in ppFEV1 at week 24 analysed in all randomised patients who received at least one dose of study drug. Both trials are registered with ClinicalTrials.gov (TRAFFIC: NCT01807923; TRANSPORT: NCT01807949). Both trials were done between April, 2013, and April, 2014. Of the 1108 patients included in the efficacy analysis, 81 patients had a ppFEV1 that decreased to lower than 40 between screening and baseline and 1016 had a ppFEV1 of 40 or higher at baseline. At screening, 730 had a ppFEV1 of less than 70, and 342 had a ppFEV1 of 70 or higher. Improvements in the absolute change from baseline at week 24 in ppFEV1 were observed with both lumacaftor/ivacaftor doses in the subgroup with baseline ppFEV1 levels lower than 40 (least-squares mean difference vs placebo was 3·7 percentage points [95% CI 0·5-6·9; p=0·024] in the lumacaftor [600 mg/day]-ivacaftor group and 3·3 percentage points [0·2-6·4; p=0·036] in the lumacaftor [400 mg/12 h]-ivacaftor group). Improvements in ppFEV1 compared with placebo were also reported in the subgroup with baseline ppFEV1 levels of 40 or higher (3·3 percentage points [2·3-4·4; p<0·0001] in the lumacaftor [600 mg per day]-ivacaftor group and 2·8 percentage points [1·7-3·8; p<0·0001] in the lumacaftor [400 mg/12 h]-ivacaftor group). Similar absolute improvements in ppFEV1 compared with placebo were observed in subgroups with screening ppFEV1 levels lower than 70 and ppFEV1 levels of 70 or higher. Increases in body-mass index and reduction in number of pulmonary exacerbation events were observed in both lumacaftor/ivacaftor dose groups compared with placebo across all lung function subgroups. Treatment was generally well tolerated, although the incidence of some respiratory adverse events was higher with lumacaftor/ivacaftor than with placebo in all subgroups. In patients with baseline ppFEV1 levels lower than 40, these adverse events included cough, dyspnoea, and abnormal respiration. These analyses confirm that lumacaftor/ivacaftor combination therapy benefits patients with cystic fibrosis homozygous for Phe508del CFTR who have varying degrees of lung function impairment. Vertex Pharmaceuticals. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparison between the Correlations of Retinal Nerve Fiber Layer Thickness Measured by Spectral Domain Optical Coherence Tomography and Visual Field Defects in Standard Automated White-on-White Perimetry versus Pulsar Perimetry.

PubMed

Alnawaiseh, Maged; Hömberg, Lisann; Eter, Nicole; Prokosch, Verena

2017-01-01

To compare the structure-function relationships between retinal nerve fiber layer thickness (RNFLT) and visual field defects measured either by standard automated perimetry (SAP) or by Pulsar perimetry (PP). 263 eyes of 143 patients were prospectively included. Depending on the RNFLT, patients were assigned to the glaucoma group (group A: RNFL score 3-6) or the control group (group B: RNFL score 0-2). Structure-function relationships between RNFLT and mean sensitivity (MS) measured by SAP and PP were analyzed. Throughout the entire group, the MS assessed by PP and SAP correlated significantly with RNFLT in all sectors. In the glaucoma group, there was no significant difference between the correlations RNFL-SAP and RNFL-PP, whereas a significant difference was found in the control group. In the control group, the correlation between structure and function based on the PP data was significantly stronger than that based on SAP.

Ascorbate protects endothelial barrier function during septic insult: Role of protein phosphatase type 2A.

PubMed

Han, Min; Pendem, Suresh; Teh, Suet Ling; Sukumaran, Dinesh K; Wu, Feng; Wilson, John X

2010-01-01

Endothelial barrier dysfunction contributes to morbidity in sepsis. We tested the hypothesis that raising the intracellular ascorbate concentration protects the endothelial barrier from septic insult by inhibiting protein phosphatase type 2A. Monolayer cultures of microvascular endothelial cells were incubated with ascorbate, dehydroascorbic acid (DHAA), the NADPH oxidase inhibitors apocynin and diphenyliodonium, or the PP2A inhibitor okadaic acid and then were exposed to septic insult (lipopolysaccharide and interferon-gamma). Under standard culture conditions that depleted intracellular ascorbate, septic insult stimulated oxidant production and PP2A activity, dephosphorylated phosphoserine and phosphothreonine residues in the tight junction-associated protein occludin, decreased the abundance of occludin at cell borders, and increased monolayer permeability to albumin. NADPH oxidase inhibitors prevented PP2A activation and monolayer leak, showing that these changes required reactive oxygen species. Okadaic acid, at a concentration that inhibited PP2A activity and monolayer leak, prevented occludin dephosphorylation and redistribution, implicating PP2A in the response of occludin to septic insult. Incubation with ascorbate or DHAA raised intracellular ascorbate concentrations and mitigated the effects of septic insult. In conclusion, ascorbate acts within microvascular endothelial cells to inhibit septic stimulation of oxidant production by NADPH oxidase and thereby prevents PP2A activation, PP2A-dependent dephosphorylation and redistribution of occludin, and disruption of the endothelial barrier. Copyright 2009 Elsevier Inc. All rights reserved.

Noninvasive Evaluation of Varying Pulse Pressures in vivo Using Brachial Sphymomanometry, Applanation Tonometry, and Pulse Wave Ultrasound Manometry.

PubMed

Li, Ronny X; Ip, Ada; Sanz-Miralles, Elena; Konofagou, Elisa E

2017-06-01

The routine assessment and monitoring of hypertension may benefit from the evaluation of arterial pulse pressure (PP) at more central locations (e.g. the aorta) rather solely at the brachial artery. Pulse Wave Ultrasound Manometry (PWUM) was previously developed by our group to provide direct, noninvasive aortic PP measurements using ultrasound elasticity imaging. Using PWUM, radial applanation tonometry, and brachial sphygmomanometry, this study investigated the feasibility of noninvasively obtaining direct PP measurements at multiple arterial locations in normotensive, pre-hypertensive, and hypertensive human subjects. Two-way ANOVA indicated a significantly higher aortic PP in the hypertensive subjects, while radial and brachial PP were not significantly different among the subject groups. No strong correlation (r 2 < 0.45) was observed between aortic and radial/brachial PP in normal and pre-hypertensive subjects, suggesting that increases in PP throughout the arterial tree may not be uniform in relatively compliant arteries. However, there was a relatively strong positive correlation between aortic PP and both radial and brachial PP in hypertensive subjects (r 2 = 0.68 and 0.87, respectively). PWUM provides a low-cost, non-invasive, and direct means of measuring the pulse pressure in large central arteries such as the aorta. When used in conjunction with peripheral measurement devices, PWUM allows for the routine screening of hypertension and monitoring of BP-lowering drugs based on the PP from multiple arterial sites.

Mitochondria-targeted catalase reduces abnormal APP processing, amyloid β production and BACE1 in a mouse model of Alzheimer's disease: implications for neuroprotection and lifespan extension.

PubMed

Mao, Peizhong; Manczak, Maria; Calkins, Marcus J; Truong, Quang; Reddy, Tejaswini P; Reddy, Arubala P; Shirendeb, Ulziibat; Lo, Herng-Hsiang; Rabinovitch, Peter S; Reddy, P Hemachandra

2012-07-01

The purpose of this study was to investigate the protective effects of the mitochondria-targeted antioxidant catalase (MCAT) and lifespan extension in mice that express amyloid beta (Aβ). Using immunoblotting and immunostaining analyses, we measured the production of full-length amyloid precursor protein (APP), soluble APPα, C-terminal fragments CTF99 and CTF83, monomeric and oligomeric Aβ, Aβ deposits and beta site amyloid precursor protein cleaving enzyme 1 (BACE1), in different stages of disease progression in MCAT/AβPP and AβPP mice. Using quantitative reverse transcriptase polymerase chain reaction and immunostaining analyses, we studied the expression of catalase, BACE1, the Alzheimer's disease (AD) markers, synaptophysin, APP, neprilysin, insulin-degrading enzyme and transthyretin in MCAT, AβPP, MCAT/AβPP and wild-type (WT) mice. Using the high pressure liquid chromatography analysis of 8-hydroxy-2-deoxyguanosine, we measured oxidative DNA damage in the cerebral cortical tissues from MCAT, AβPP, MCAT/AβPP and WT mice. We found that the AβPP transgenic mice that carried the human MCAT gene lived 5 months longer than did the AβPP mice. We also found that the overexpression of MCAT in the brain sections from the MCAT/AβPP transgenic mice significantly correlated with a reduction in the levels of full-length APP, CTF99, BACE1, Aβ levels (40 and 42), Aβ deposits and oxidative DNA damage relative to the brain sections from the AβPP mice. Interestingly, we found significantly increased levels of soluble APPα and CTF83 in the MCAT/AβPP mice, relative to the AβPP mice. These data provide direct evidence that oxidative stress plays a primary role in AD etiopathology and that in MCAT mice express Aβ, MCAT prevents abnormal APP processing, reduces Aβ levels and enhances Aβ-degrading enzymes in mice at different ages, corresponding to different stages of disease progression. These findings indicate that mitochondria-targeted molecules may be an effective therapeutic approach to treat patients with AD.

Mitochondria-targeted catalase reduces abnormal APP processing, amyloid β production and BACE1 in a mouse model of Alzheimer's disease: implications for neuroprotection and lifespan extension

PubMed Central

Mao, Peizhong; Manczak, Maria; Calkins, Marcus J.; Truong, Quang; Reddy, Tejaswini P.; Reddy, Arubala P.; Shirendeb, Ulziibat; Lo, Herng-Hsiang; Rabinovitch, Peter S.; Reddy, P. Hemachandra

2012-01-01

The purpose of this study was to investigate the protective effects of the mitochondria-targeted antioxidant catalase (MCAT) and lifespan extension in mice that express amyloid beta (Aβ). Using immunoblotting and immunostaining analyses, we measured the production of full-length amyloid precursor protein (APP), soluble APPα, C-terminal fragments CTF99 and CTF83, monomeric and oligomeric Aβ, Aβ deposits and beta site amyloid precursor protein cleaving enzyme 1 (BACE1), in different stages of disease progression in MCAT/AβPP and AβPP mice. Using quantitative reverse transcriptase polymerase chain reaction and immunostaining analyses, we studied the expression of catalase, BACE1, the Alzheimer's disease (AD) markers, synaptophysin, APP, neprilysin, insulin-degrading enzyme and transthyretin in MCAT, AβPP, MCAT/AβPP and wild-type (WT) mice. Using the high pressure liquid chromatography analysis of 8-hydroxy-2-deoxyguanosine, we measured oxidative DNA damage in the cerebral cortical tissues from MCAT, AβPP, MCAT/AβPP and WT mice. We found that the AβPP transgenic mice that carried the human MCAT gene lived 5 months longer than did the AβPP mice. We also found that the overexpression of MCAT in the brain sections from the MCAT/AβPP transgenic mice significantly correlated with a reduction in the levels of full-length APP, CTF99, BACE1, Aβ levels (40 and 42), Aβ deposits and oxidative DNA damage relative to the brain sections from the AβPP mice. Interestingly, we found significantly increased levels of soluble APPα and CTF83 in the MCAT/AβPP mice, relative to the AβPP mice. These data provide direct evidence that oxidative stress plays a primary role in AD etiopathology and that in MCAT mice express Aβ, MCAT prevents abnormal APP processing, reduces Aβ levels and enhances Aβ-degrading enzymes in mice at different ages, corresponding to different stages of disease progression. These findings indicate that mitochondria-targeted molecules may be an effective therapeutic approach to treat patients with AD. PMID:22492996

Redescription of the Holotype of Culex (Culex) Peus Speiser and Taxonomy of Culex (Culex) Stigmatosoma Dyar and Thriambus Dyar (Diptera: Culicidae)

DTIC Science & Technology

1988-10-12

Ver- teneuil, Brussels. 257 pp. + 5 pls. Forattini, 0. P. 1965. Entomologia Medica. 2” Vol- ume_ Editora da Universidade de Sao Paulo. 506 PP...Publica, Boletines T&r& cos, Serie A: Entomologia Medica y Parasitologia No. 1. 66 pp. Matheson, R. 1944. Handbook of the Mosquitoes of North America

Long-term ecological effects of exposure to uranium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hanson, W.C.; Miera, F.R. Jr.

1976-03-01

The consequences of releasing natural and depleted uranium to terrestrial ecosystems during development and testing of depleted uranium munitions were investigated. At Eglin Air Force Base, Florida, soil at various distances from armor plate target butts struck by depleted uranium penetrators was sampled. The upper 5 cm of soil at the target bases contained an average of 800 ppM of depleted uranium, about 30 times as much as soil at 5- to 10-cm depth, indicating some vertical movement of depleted uranium. Samples collected beyond about 20 m from the targets showed near-background natural uranium levels, about 1.3 +- 0.3 ..mu..g/gmore » or ppM. Two explosives-testing areas at the Los Alamos Scientific Laboratory (LASL) were selected because of their use history. E-F Site soil averaged 2400 ppM of uranium in the upper 5 cm and 1600 ppM at 5-10 cm. Lower Slobovia Site soil from two subplots averaged about 2.5 and 0.6 percent of the E-F Site concentrations. Important uranium concentration differences with depth and distance from detonation points were ascribed to the different explosive tests conducted in each area. E-F Site vegetation samples contained about 320 ppM of uranium in November 1974 and about 125 ppM in June 1975. Small mammals trapped in the study areas in November contained a maximum of 210 ppM of uranium in the gastrointestinal tract contents, 24 ppM in the pelt, and 4 ppM in the remaining carcass. In June, maximum concentrations were 110, 50, and 2 ppM in similar samples and 6 ppM in lungs. These data emphasized the importance of resuspension of respirable particles in the upper few millimeters of soil as a contamination mechanism for several components of the LASL ecosystem.« less

Bioaccessibility of polyphenols associated with dietary fiber and in vitro kinetics release of polyphenols in Mexican 'Ataulfo' mango (Mangifera indica L.) by-products.

PubMed

Blancas-Benitez, Francisco J; Mercado-Mercado, Gilberto; Quirós-Sauceda, Ana E; Montalvo-González, Efigenia; González-Aguilar, Gustavo A; Sáyago-Ayerdi, Sonia G

2015-03-01

The biological properties of polyphenol (PP) depend on its bioaccessibility and bioavailability. Therefore, part of PP released from the food matrix in the gastrointestinal tract through enzymatic hydrolysis is at least partially absorbed. The aim of this study is to determine the bioaccessibility of PP associated with dietary fiber (DF) and the kinetics release of PP in mango (Mangifera indica L.) 'Ataulfo' by-products by an in vitro model. Soluble and insoluble DF values were 7.99 and 18.56% in the mango paste and 6.98 and 22.78% in the mango peel, respectively. PP associated with soluble and insoluble DF was 6.0 and 3.73 g GAE per 100 g in the paste and 4.72 and 4.50 g GAE per 100 g in the peel. The bioaccessibility of PP was 38.67% in the pulp paste and 40.53% in the peel. A kinetics study shows a release rate of 2.66 and 3.27 g PP min(-1) in the paste and peel, respectively. The antioxidant capacity of the paste increased as digestion reached a value of 2.87 mmol TE min(-1) at 180 min. The antioxidant capacity of the peel had its maximum (28.94 mmol TE min(-1)) between 90 and 120 min of digestion; it started with a value of 2.58 mmol TE min(-1), and thereafter increased to 4.20 mmol TE min(-1) at 180 min. The major PPs released during the digestion of paste were gallic and hydroxybenzoic acids, while in the peel, they were hydroxycinnamic and vanillic acids. It was concluded that these phenolic compounds are readily available for absorption in the small intestine and exert different potential health benefits.

Relative Modification of Prompt ψ(2S) and J/ψ Yields from pp to PbPb Collisions at sqrt[s_{NN}]=5.02  TeV.

PubMed

Sirunyan, A M; Tumasyan, A; Adam, W; Asilar, E; Bergauer, T; Brandstetter, J; Brondolin, E; Dragicevic, M; Erö, J; Flechl, M; Friedl, M; Frühwirth, R; Ghete, V M; Hartl, C; Hörmann, N; Hrubec, J; Jeitler, M; König, A; Krätschmer, I; Liko, D; Matsushita, T; Mikulec, I; Rabady, D; Rad, N; Rahbaran, B; Rohringer, H; Schieck, J; Strauss, J; Waltenberger, W; Wulz, C-E; Chekhovsky, V; Dvornikov, O; Dydyshka, Y; Emeliantchik, I; Litomin, A; Makarenko, V; Mossolov, V; Stefanovitch, R; Suarez Gonzalez, J; Zykunov, V; Shumeiko, N; Alderweireldt, S; De Wolf, E A; Janssen, X; Lauwers, J; Van De Klundert, M; Van Haevermaet, H; Van Mechelen, P; Van Remortel, N; Van Spilbeeck, A; Abu Zeid, S; Blekman, F; D'Hondt, J; Daci, N; De Bruyn, I; Deroover, K; Lowette, S; Moortgat, S; Moreels, L; Olbrechts, A; Python, Q; Skovpen, K; Tavernier, S; Van Doninck, W; Van Mulders, P; Van Parijs, I; Brun, H; Clerbaux, B; De Lentdecker, G; Delannoy, H; Fasanella, G; Favart, L; Goldouzian, R; Grebenyuk, A; Karapostoli, G; Lenzi, T; Léonard, A; Luetic, J; Maerschalk, T; Marinov, A; Randle-Conde, A; Seva, T; Vander Velde, C; Vanlaer, P; Vannerom, D; Yonamine, R; Zenoni, F; Zhang, F; Cimmino, A; Cornelis, T; Dobur, D; Fagot, A; Garcia, G; Gul, M; Khvastunov, I; Poyraz, D; Salva, S; Schöfbeck, R; Tytgat, M; Van Driessche, W; Yazgan, E; Zaganidis, N; Bakhshiansohi, H; Beluffi, C; Bondu, O; Brochet, S; Bruno, G; Caudron, A; De Visscher, S; Delaere, C; Delcourt, M; Francois, B; Giammanco, A; Jafari, A; Jez, P; Komm, M; Krintiras, G; Lemaitre, V; Magitteri, A; Mertens, A; Musich, M; Nuttens, C; Piotrzkowski, K; Quertenmont, L; Selvaggi, M; Vidal Marono, M; Wertz, S; Beliy, N; Aldá Júnior, W L; Alves, F L; Alves, G A; Brito, L; Hensel, C; Moraes, A; Pol, M E; Rebello Teles, P; Belchior Batista Das Chagas, E; Carvalho, W; Chinellato, J; Custódio, A; Da Costa, E M; Da Silveira, G G; De Jesus Damiao, D; De Oliveira Martins, C; Fonseca De Souza, S; Huertas Guativa, L M; Malbouisson, H; Matos Figueiredo, D; Mora Herrera, C; Mundim, L; Nogima, H; Prado Da Silva, W L; Santoro, A; Sznajder, A; Tonelli Manganote, E J; Vilela Pereira, A; Ahuja, S; Bernardes, C A; Dogra, S; Tomei, T R Fernandez Perez; Gregores, E M; Mercadante, P G; Moon, C S; Novaes, S F; Padula, Sandra S; Romero Abad, D; Ruiz Vargas, J C; Aleksandrov, A; Hadjiiska, R; Iaydjiev, P; Rodozov, M; Stoykova, S; Sultanov, G; Vutova, M; Dimitrov, A; Glushkov, I; Litov, L; Pavlov, B; Petkov, P; Fang, W; Ahmad, M; Bian, J G; Chen, G M; Chen, H S; Chen, M; Chen, Y; Cheng, T; Jiang, C H; Leggat, D; Liu, Z; Romeo, F; Shaheen, S M; Spiezia, A; Tao, J; Wang, C; Wang, Z; Zhang, H; Zhao, J; Ban, Y; Chen, G; Li, Q; Liu, S; Mao, Y; Qian, S J; Wang, D; Xu, Z; Avila, C; Cabrera, A; Chaparro Sierra, L F; Florez, C; Gomez, J P; González Hernández, C F; Ruiz Alvarez, J D; Sanabria, J C; Godinovic, N; Lelas, D; Puljak, I; Ribeiro Cipriano, P M; Sculac, T; Antunovic, Z; Kovac, M; Brigljevic, V; Ferencek, D; Kadija, K; Mesic, B; Micanovic, S; Sudic, L; Susa, T; Attikis, A; Mavromanolakis, G; Mousa, J; Nicolaou, C; Ptochos, F; Razis, P A; Rykaczewski, H; Tsiakkouri, D; Finger, M; Finger, M; Carrera Jarrin, E; Ellithi Kamel, A; Mahmoud, M A; Radi, A; Kadastik, M; Perrini, L; Raidal, M; Tiko, A; Veelken, C; Eerola, P; Pekkanen, J; Voutilainen, M; Härkönen, J; Järvinen, T; Karimäki, V; Kinnunen, R; Lampén, T; Lassila-Perini, K; Lehti, S; Lindén, T; Luukka, P; Tuominiemi, J; Tuovinen, E; Wendland, L; Talvitie, J; Tuuva, T; Besancon, M; Couderc, F; Dejardin, M; Denegri, D; Fabbro, B; Faure, J L; Favaro, C; Ferri, F; Ganjour, S; Ghosh, S; Givernaud, A; Gras, P; Hamel de Monchenault, G; Jarry, P; Kucher, I; Locci, E; Machet, M; Malcles, J; Rander, J; Rosowsky, A; Titov, M; Zghiche, A; Abdulsalam, A; Antropov, I; Arleo, F; Baffioni, S; Beaudette, F; Busson, P; Cadamuro, L; Chapon, E; Charlot, C; Davignon, O; Granier de Cassagnac, R; Jo, M; Lisniak, S; Martin Blanco, J; Miné, P; Nguyen, M; Ochando, C; Ortona, G; Paganini, P; Pigard, P; Regnard, S; Salerno, R; Sirois, Y; Stahl Leiton, A G; Strebler, T; Yilmaz, Y; Zabi, A; Agram, J-L; Andrea, J; Aubin, A; Bloch, D; Brom, J-M; Buttignol, M; Chabert, E C; Chanon, N; Collard, C; Conte, E; Coubez, X; Fontaine, J-C; Gelé, D; Goerlach, U; Le Bihan, A-C; Van Hove, P; Gadrat, S; Beauceron, S; Bernet, C; Boudoul, G; Carrillo Montoya, C A; Chierici, R; Contardo, D; Courbon, B; Depasse, P; El Mamouni, H; Fan, J; Fay, J; Gascon, S; Gouzevitch, M; Grenier, G; Ille, B; Lagarde, F; Laktineh, I B; Lethuillier, M; Mirabito, L; Pequegnot, A L; Perries, S; Popov, A; Sabes, D; Sordini, V; Vander Donckt, M; Verdier, P; Viret, S; Toriashvili, T; Tsamalaidze, Z; Autermann, C; Beranek, S; Feld, L; Kiesel, M K; Klein, K; Lipinski, M; Preuten, M; Schael, S; Schomakers, C; Schulz, J; Verlage, T; Albert, A; Brodski, M; Dietz-Laursonn, E; Duchardt, D; Endres, M; Erdmann, M; Erdweg, S; Esch, T; Fischer, R; Güth, A; Hamer, M; Hebbeker, T; Heidemann, C; Hoepfner, K; Knutzen, S; Merschmeyer, M; Meyer, A; Millet, P; Mukherjee, S; Olschewski, M; Padeken, K; Pook, T; Radziej, M; Reithler, H; Rieger, M; Scheuch, F; Sonnenschein, L; Teyssier, D; Thüer, S; Cherepanov, V; Flügge, G; Kargoll, B; Kress, T; Künsken, A; Lingemann, J; Müller, T; Nehrkorn, A; Nowack, A; Pistone, C; Pooth, O; Stahl, A; Aldaya Martin, M; Arndt, T; Asawatangtrakuldee, C; Beernaert, K; Behnke, O; Behrens, U; Bin Anuar, A A; Borras, K; Campbell, A; Connor, P; Contreras-Campana, C; Costanza, F; Diez Pardos, C; Dolinska, G; Eckerlin, G; Eckstein, D; Eichhorn, T; Eren, E; Gallo, E; Garay Garcia, J; Geiser, A; Gizhko, A; Grados Luyando, J M; Grohsjean, A; Gunnellini, P; Harb, A; Hauk, J; Hempel, M; Jung, H; Kalogeropoulos, A; Karacheban, O; Kasemann, M; Keaveney, J; Kleinwort, C; Korol, I; Krücker, D; Lange, W; Lelek, A; Leonard, J; Lipka, K; Lobanov, A; Lohmann, W; Mankel, R; Melzer-Pellmann, I-A; Meyer, A B; Mittag, G; Mnich, J; Mussgiller, A; Ntomari, E; Pitzl, D; Placakyte, R; Raspereza, A; Roland, B; Sahin, M Ö; Saxena, P; Schoerner-Sadenius, T; Seitz, C; Spannagel, S; Stefaniuk, N; Van Onsem, G P; Walsh, R; Wissing, C; Blobel, V; Centis Vignali, M; Draeger, A R; Dreyer, T; Garutti, E; Gonzalez, D; Haller, J; Hoffmann, M; Junkes, A; Klanner, R; Kogler, R; Kovalchuk, N; Lapsien, T; Lenz, T; Marchesini, I; Marconi, D; Meyer, M; Niedziela, M; Nowatschin, D; Pantaleo, F; Peiffer, T; Perieanu, A; Poehlsen, J; Sander, C; Scharf, C; Schleper, P; Schmidt, A; Schumann, S; Schwandt, J; Stadie, H; Steinbrück, G; Stober, F M; Stöver, M; Tholen, H; Troendle, D; Usai, E; Vanelderen, L; Vanhoefer, A; Vormwald, B; Akbiyik, M; Barth, C; Baur, S; Baus, C; Berger, J; Butz, E; Caspart, R; Chwalek, T; Colombo, F; De Boer, W; Dierlamm, A; Fink, S; Freund, B; Friese, R; Giffels, M; Gilbert, A; Goldenzweig, P; Haitz, D; Hartmann, F; Heindl, S M; Husemann, U; Katkov, I; Kudella, S; Mildner, H; Mozer, M U; Müller, Th; Plagge, M; Quast, G; Rabbertz, K; Röcker, S; Roscher, F; Schröder, M; Shvetsov, I; Sieber, G; Simonis, H J; Ulrich, R; Wayand, S; Weber, M; Weiler, T; Williamson, S; Wöhrmann, C; Wolf, R; Anagnostou, G; Daskalakis, G; Geralis, T; Giakoumopoulou, V A; Kyriakis, A; Loukas, D; Topsis-Giotis, I; Kesisoglou, S; Panagiotou, A; Saoulidou, N; Tziaferi, E; Evangelou, I; Flouris, G; Foudas, C; Kokkas, P; Loukas, N; Manthos, N; Papadopoulos, I; Paradas, E; Filipovic, N; Bencze, G; Hajdu, C; Horvath, D; Sikler, F; Veszpremi, V; Vesztergombi, G; Zsigmond, A J; Beni, N; Czellar, S; Karancsi, J; Makovec, A; Molnar, J; Szillasi, Z; Bartók, M; Raics, P; Trocsanyi, Z L; Ujvari, B; Bahinipati, S; Choudhury, S; Mal, P; Mandal, K; Nayak, A; Sahoo, D K; Sahoo, N; Swain, S K; Bansal, S; Beri, S B; Bhatnagar, V; Chawla, R; Bhawandeep, U; Kalsi, A K; Kaur, A; Kaur, M; Kumar, R; Kumari, P; Mehta, A; Mittal, M; Singh, J B; Walia, G; Kumar, Ashok; Bhardwaj, A; Choudhary, B C; Garg, R B; Keshri, S; Malhotra, S; Naimuddin, M; Nishu, N; Ranjan, K; Sharma, R; Sharma, V; Bhattacharya, R; Bhattacharya, S; Chatterjee, K; Dey, S; Dutt, S; Dutta, S; Ghosh, S; Majumdar, N; Modak, A; Mondal, K; Mukhopadhyay, S; Nandan, S; Purohit, A; Roy, A; Roy, D; Roy Chowdhury, S; Sarkar, S; Sharan, M; Thakur, S; Behera, P K; Chudasama, R; Dutta, D; Jha, V; Kumar, V; Mohanty, A K; Netrakanti, P K; Pant, L M; Shukla, P; Topkar, A; Aziz, T; Dugad, S; Kole, G; Mahakud, B; Mitra, S; Mohanty, G B; Parida, B; Sur, N; Sutar, B; Banerjee, S; Bhowmik, S; Dewanjee, R K; Ganguly, S; Guchait, M; Jain, Sa; Kumar, S; Maity, M; Majumder, G; Mazumdar, K; Sarkar, T; Wickramage, N; Chauhan, S; Dube, S; Hegde, V; Kapoor, A; Kothekar, K; Pandey, S; Rane, A; Sharma, S; Chenarani, S; Eskandari Tadavani, E; Etesami, S M; Fahim, A; Khakzad, M; Mohammadi Najafabadi, M; Naseri, M; Paktinat Mehdiabadi, S; Rezaei Hosseinabadi, F; Safarzadeh, B; Zeinali, M; Felcini, M; Grunewald, M; Abbrescia, M; Calabria, C; Caputo, C; Colaleo, A; Creanza, D; Cristella, L; De Filippis, N; De Palma, M; Fiore, L; Iaselli, G; Maggi, G; Maggi, M; Miniello, G; My, S; Nuzzo, S; Pompili, A; Pugliese, G; Radogna, R; Ranieri, A; Selvaggi, G; Sharma, A; Silvestris, L; Venditti, R; Verwilligen, P; Abbiendi, G; Battilana, C; Bonacorsi, D; Braibant-Giacomelli, S; Brigliadori, L; Campanini, R; Capiluppi, P; Castro, A; Cavallo, F R; Chhibra, S S; Codispoti, G; Cuffiani, M; Dallavalle, G M; Fabbri, F; Fanfani, A; Fasanella, D; Giacomelli, P; Grandi, C; Guiducci, L; Marcellini, S; Masetti, G; Montanari, A; Navarria, F L; Perrotta, A; Rossi, A M; Rovelli, T; Siroli, G P; Tosi, N; Albergo, S; Costa, S; Di Mattia, A; Giordano, F; Potenza, R; Tricomi, A; Tuve, C; Barbagli, G; Ciulli, V; Civinini, C; D'Alessandro, R; Focardi, E; Lenzi, P; Meschini, M; Paoletti, S; Sguazzoni, G; Viliani, L; Benussi, L; Bianco, S; Fabbri, F; Piccolo, D; Primavera, F; Calvelli, V; Ferro, F; Lo Vetere, M; Monge, M R; Robutti, E; Tosi, S; Brianza, L; Brivio, F; Dinardo, M E; Fiorendi, S; Gennai, S; Ghezzi, A; Govoni, P; Malberti, M; Malvezzi, S; Manzoni, R A; Menasce, D; Moroni, L; Paganoni, M; Pedrini, D; Pigazzini, S; Ragazzi, S; Tabarelli de Fatis, T; Buontempo, S; Cavallo, N; De Nardo, G; Di Guida, S; Esposito, M; Fabozzi, F; Fienga, F; Iorio, A O M; Lanza, G; Lista, L; Meola, S; Paolucci, P; Sciacca, C; Thyssen, F; Azzi, P; Bacchetta, N; Benato, L; Bisello, D; Boletti, A; Carlin, R; Carvalho Antunes De Oliveira, A; Checchia, P; Dall'Osso, M; De Castro Manzano, P; Dorigo, T; Dosselli, U; Gasparini, F; Gasparini, U; Gozzelino, A; Lacaprara, S; Margoni, M; Meneguzzo, A T; Pazzini, J; Pozzobon, N; Ronchese, P; Simonetto, F; Torassa, E; Zanetti, M; Zotto, P; Zumerle, G; Braghieri, A; Magnani, A; Montagna, P; Ratti, S P; Re, V; Riccardi, C; Salvini, P; Vai, I; Vitulo, P; Alunni Solestizi, L; Bilei, G M; Ciangottini, D; Fanò, L; Lariccia, P; Leonardi, R; Mantovani, G; Menichelli, M; Saha, A; Santocchia, A; Androsov, K; Azzurri, P; Bagliesi, G; Bernardini, J; Boccali, T; Castaldi, R; Ciocci, M A; Dell'Orso, R; Donato, S; Fedi, G; Giassi, A; Grippo, M T; Ligabue, F; Lomtadze, T; Martini, L; Messineo, A; Palla, F; Rizzi, A; Savoy-Navarro, A; Spagnolo, P; Tenchini, R; Tonelli, G; Venturi, A; Verdini, P G; Barone, L; Cavallari, F; Cipriani, M; Del Re, D; Diemoz, M; Gelli, S; Longo, E; Margaroli, F; Marzocchi, B; Meridiani, P; Organtini, G; Paramatti, R; Preiato, F; Rahatlou, S; Rovelli, C; Santanastasio, F; Amapane, N; Arcidiacono, R; Argiro, S; Arneodo, M; Bartosik, N; Bellan, R; Biino, C; Cartiglia, N; Cenna, F; Costa, M; Covarelli, R; Degano, A; Demaria, N; Finco, L; Kiani, B; Mariotti, C; Maselli, S; Migliore, E; Monaco, V; Monteil, E; Monteno, M; Obertino, M M; Pacher, L; Pastrone, N; Pelliccioni, M; Pinna Angioni, G L; Ravera, F; Romero, A; Ruspa, M; Sacchi, R; Shchelina, K; Sola, V; Solano, A; Staiano, A; Traczyk, P; Belforte, S; Casarsa, M; Cossutti, F; Della Ricca, G; Zanetti, A; Kim, D H; Kim, G N; Kim, M S; Lee, S; Lee, S W; Oh, Y D; Sekmen, S; Son, D C; Yang, Y C; Lee, A; Kim, H; Brochero Cifuentes, J A; Kim, T J; Cho, S; Choi, S; Go, Y; Gyun, D; Ha, S; Hong, B; Jo, Y; Kim, Y; Lee, B; Lee, K; Lee, K S; Lee, S; Lim, J; Park, S K; Roh, Y; Almond, J; Kim, J; Lee, H; Oh, S B; Radburn-Smith, B C; Seo, S H; Yang, U K; Yoo, H D; Yu, G B; Choi, M; Kim, H; Kim, J H; Lee, J S H; Park, I C; Ryu, G; Ryu, M S; Choi, Y; Goh, J; Hwang, C; Lee, J; Yu, I; Dudenas, V; Juodagalvis, A; Vaitkus, J; Ahmed, I; Ibrahim, Z A; Komaragiri, J R; Md Ali, M A B; Mohamad Idris, F; Wan Abdullah, W A T; Yusli, M N; Zolkapli, Z; Castilla-Valdez, H; De La Cruz-Burelo, E; Heredia-De La Cruz, I; Hernandez-Almada, A; Lopez-Fernandez, R; Magaña Villalba, R; Mejia Guisao, J; Sanchez-Hernandez, A; Carrillo Moreno, S; Oropeza Barrera, C; Vazquez Valencia, F; Carpinteyro, S; Pedraza, I; Salazar Ibarguen, H A; Uribe Estrada, C; Morelos Pineda, A; Krofcheck, D; Butler, P H; Ahmad, A; Ahmad, M; Hassan, Q; Hoorani, H R; Khan, W A; Saddique, A; Shah, M A; Shoaib, M; Waqas, M; Bialkowska, H; Bluj, M; Boimska, B; Frueboes, T; Górski, M; Kazana, M; Nawrocki, K; Romanowska-Rybinska, K; Szleper, M; Zalewski, P; Bunkowski, K; Byszuk, A; Doroba, K; Kalinowski, A; Konecki, M; Krolikowski, J; Misiura, M; Olszewski, M; Walczak, M; Bargassa, P; Beirão Da Cruz E Silva, C; Calpas, B; Di Francesco, A; Faccioli, P; Ferreira Parracho, P G; Gallinaro, M; Hollar, J; Leonardo, N; Lloret Iglesias, L; Nemallapudi, M V; Rodrigues Antunes, J; Seixas, J; Toldaiev, O; Vadruccio, D; Varela, J; Vischia, P; Afanasiev, S; Bunin, P; Gavrilenko, M; Golutvin, I; Gorbunov, I; Kamenev, A; Karjavin, V; Lanev, A; Malakhov, A; Matveev, V; Palichik, V; Perelygin, V; Shmatov, S; Shulha, S; Skatchkov, N; Smirnov, V; Voytishin, N; Zarubin, A; Chtchipounov, L; Golovtsov, V; Ivanov, Y; Kim, V; Kuznetsova, E; Murzin, V; Oreshkin, V; Sulimov, V; Vorobyev, A; Andreev, Yu; Dermenev, A; Gninenko, S; Golubev, N; Karneyeu, A; Kirsanov, M; Krasnikov, N; Pashenkov, A; Tlisov, D; Toropin, A; Epshteyn, V; Gavrilov, V; Lychkovskaya, N; Popov, V; Pozdnyakov, I; Safronov, G; Spiridonov, A; Toms, M; Vlasov, E; Zhokin, A; Bylinkin, A; Chistov, R; Markin, O; Polikarpov, S; Andreev, V; Azarkin, M; Dremin, I; Kirakosyan, M; Leonidov, A; Terkulov, A; Baskakov, A; Belyaev, A; Boos, E; Ershov, A; Gribushin, A; Kaminskiy, A; Kodolova, O; Korotkikh, V; Lokhtin, I; Miagkov, I; Obraztsov, S; Petrushanko, S; Savrin, V; Snigirev, A; Vardanyan, I; Blinov, V; Skovpen, Y; Shtol, D; Azhgirey, I; Bayshev, I; Bitioukov, S; Elumakhov, D; Kachanov, V; Kalinin, A; Konstantinov, D; Krychkine, V; Petrov, V; Ryutin, R; Sobol, A; Troshin, S; Tyurin, N; Uzunian, A; Volkov, A; Adzic, P; Cirkovic, P; Devetak, D; Dordevic, M; Milosevic, J; Rekovic, V; Alcaraz Maestre, J; Barrio Luna, M; Calvo, E; Cerrada, M; Chamizo Llatas, M; Colino, N; De La Cruz, B; Delgado Peris, A; Escalante Del Valle, A; Fernandez Bedoya, C; Fernández Ramos, J P; Flix, J; Fouz, M C; Garcia-Abia, P; Gonzalez Lopez, O; Goy Lopez, S; Hernandez, J M; Josa, M I; Navarro De Martino, E; Pérez-Calero Yzquierdo, A; Puerta Pelayo, J; Quintario Olmeda, A; Redondo, I; Romero, L; Soares, M S; de Trocóniz, J F; Missiroli, M; Moran, D; Cuevas, J; Fernandez Menendez, J; Gonzalez Caballero, I; González Fernández, J R; Palencia Cortezon, E; Sanchez Cruz, S; Suárez Andrés, I; Vizan Garcia, J M; Cabrillo, I J; Calderon, A; Castiñeiras De Saa, J R; Curras, E; Fernandez, M; Garcia-Ferrero, J; Gomez, G; Lopez Virto, A; Marco, J; Martinez Rivero, C; Matorras, F; Piedra Gomez, J; Rodrigo, T; Ruiz-Jimeno, A; Scodellaro, L; Trevisani, N; Vila, I; Vilar Cortabitarte, R; Abbaneo, D; Auffray, E; Auzinger, G; Bachtis, M; Baillon, P; Ball, A H; Barney, D; Bloch, P; Bocci, A; Bonato, A; Botta, C; Camporesi, T; Castello, R; Cepeda, M; Cerminara, G; d'Enterria, D; Dabrowski, A; Daponte, V; David, A; De Gruttola, M; De Roeck, A; Di Marco, E; Dobson, M; Dorney, B; du Pree, T; Duggan, D; Dünser, M; Dupont, N; Elliott-Peisert, A; Everaerts, P; Fartoukh, S; Franzoni, G; Fulcher, J; Funk, W; Gigi, D; Gill, K; Girone, M; Glege, F; Gulhan, D; Gundacker, S; Guthoff, M; Hammer, J; Harris, P; Hegeman, J; Innocente, V; Janot, P; Kieseler, J; Kirschenmann, H; Knünz, V; Kornmayer, A; Kortelainen, M J; Kousouris, K; Krammer, M; Lange, C; Lecoq, P; Lourenço, C; Lucchini, M T; Malgeri, L; Mannelli, M; Martelli, A; Meijers, F; Merlin, J A; Mersi, S; Meschi, E; Milenovic, P; Moortgat, F; Morovic, S; Mulders, M; Neugebauer, H; Orfanelli, S; Orsini, L; Pape, L; Perez, E; Peruzzi, M; Petrilli, A; Petrucciani, G; Pfeiffer, A; Pierini, M; Racz, A; Reis, T; Rolandi, G; Rovere, M; Ruan, M; Sakulin, H; Sauvan, J B; Schäfer, C; Schwick, C; Seidel, M; Sharma, A; Silva, P; Sphicas, P; Steggemann, J; Stoye, M; Takahashi, Y; Tosi, M; Treille, D; Triossi, A; Tsirou, A; Veckalns, V; Veres, G I; Verweij, M; Wardle, N; Wöhri, H K; Zagozdzinska, A; Zeuner, W D; Bertl, W; Deiters, K; Erdmann, W; Horisberger, R; Ingram, Q; Kaestli, H C; Kotlinski, D; Langenegger, U; Rohe, T; Bachmair, F; Bäni, L; Bianchini, L; Casal, B; Dissertori, G; Dittmar, M; Donegà, M; Grab, C; Heidegger, C; Hits, D; Hoss, J; Kasieczka, G; Lecomte, P; Lustermann, W; Mangano, B; Marionneau, M; Martinez Ruiz Del Arbol, P; Masciovecchio, M; Meinhard, M T; Meister, D; Micheli, F; Musella, P; Nessi-Tedaldi, F; Pandolfi, F; Pata, J; Pauss, F; Perrin, G; Perrozzi, L; Quittnat, M; Rossini, M; Schönenberger, M; Starodumov, A; Tavolaro, V R; Theofilatos, K; Wallny, R; Aarrestad, T K; Amsler, C; Caminada, L; Canelli, M F; De Cosa, A; Galloni, C; Hinzmann, A; Hreus, T; Kilminster, B; Ngadiuba, J; Pinna, D; Rauco, G; Robmann, P; Salerno, D; Yang, Y; Zucchetta, A; Candelise, V; Doan, T H; Jain, Sh; Khurana, R; Konyushikhin, M; Kuo, C M; Lin, W; Lu, Y J; Pozdnyakov, A; Yu, S S; Kumar, Arun; Chang, P; Chang, Y H; Chang, Y W; Chao, Y; Chen, K F; Chen, P H; Dietz, C; Fiori, F; Hou, W-S; Hsiung, Y; Liu, Y F; Lu, R-S; Miñano Moya, M; Paganis, E; Psallidas, A; Tsai, J F; Tzeng, Y M; Asavapibhop, B; Singh, G; Srimanobhas, N; Suwonjandee, N; Adiguzel, A; Cerci, S; Damarseckin, S; Demiroglu, Z S; Dozen, C; Dumanoglu, I; Girgis, S; Gokbulut, G; Guler, Y; Hos, I; Kangal, E E; Kara, O; Kayis Topaksu, A; Kiminsu, U; Oglakci, M; Onengut, G; Ozdemir, K; Sunar Cerci, D; Tali, B; Turkcapar, S; Zorbakir, I S; Zorbilmez, C; Bilin, B; Bilmis, S; Isildak, B; Karapinar, G; Yalvac, M; Zeyrek, M; Gülmez, E; Kaya, M; Kaya, O; Yetkin, E A; Yetkin, T; Cakir, A; Cankocak, K; Sen, S; Grynyov, B; Levchuk, L; Sorokin, P; Aggleton, R; Ball, F; Beck, L; Brooke, J J; Burns, D; Clement, E; Cussans, D; Flacher, H; Goldstein, J; Grimes, M; Heath, G P; Heath, H F; Jacob, J; Kreczko, L; Lucas, C; Newbold, D M; Paramesvaran, S; Poll, A; Sakuma, T; Seif El Nasr-Storey, S; Smith, D; Smith, V J; Belyaev, A; Brew, C; Brown, R M; Calligaris, L; Cieri, D; Cockerill, D J A; Coughlan, J A; Harder, K; Harper, S; Olaiya, E; Petyt, D; Shepherd-Themistocleous, C H; Thea, A; Tomalin, I R; Williams, T; Baber, M; Bainbridge, R; Buchmuller, O; Bundock, A; Burton, D; Casasso, S; Citron, M; Colling, D; Corpe, L; Dauncey, P; Davies, G; De Wit, A; Della Negra, M; Di Maria, R; Dunne, P; Elwood, A; Futyan, D; Haddad, Y; Hall, G; Iles, G; James, T; Lane, R; Laner, C; Lucas, R; Lyons, L; Magnan, A-M; Malik, S; Mastrolorenzo, L; Nash, J; Nikitenko, A; Pela, J; Penning, B; Pesaresi, M; Raymond, D M; Richards, A; Rose, A; Seez, C; Summers, S; Tapper, A; Uchida, K; Vazquez Acosta, M; Virdee, T; Wright, J; Zenz, S C; Cole, J E; Hobson, P R; Khan, A; Kyberd, P; Leslie, D; Reid, I D; Symonds, P; Teodorescu, L; Turner, M; Borzou, A; Call, K; Dittmann, J; Hatakeyama, K; Liu, H; Pastika, N; Cooper, S I; Henderson, C; Rumerio, P; West, C; Arcaro, D; Avetisyan, A; Bose, T; Gastler, D; Rankin, D; Richardson, C; Rohlf, J; Sulak, L; Zou, D; Benelli, G; Berry, E; Cutts, D; Garabedian, A; Hakala, J; Heintz, U; Hogan, J M; Jesus, O; Kwok, K H M; Laird, E; Landsberg, G; Mao, Z; Narain, M; Piperov, S; Sagir, S; Spencer, E; Syarif, R; Breedon, R; Breto, G; Burns, D; Calderon De La Barca Sanchez, M; Chauhan, S; Chertok, M; Conway, J; Conway, R; Cox, P T; Erbacher, R; Flores, C; Funk, G; Gardner, M; Ko, W; Lander, R; Mclean, C; Mulhearn, M; Pellett, D; Pilot, J; Shalhout, S; Smith, J; Squires, M; Stolp, D; Tripathi, M; Bravo, C; Cousins, R; Dasgupta, A; Florent, A; Hauser, J; Ignatenko, M; Mccoll, N; Saltzberg, D; Schnaible, C; Takasugi, E; Valuev, V; Weber, M; Bouvier, E; Burt, K; Clare, R; Ellison, J; Gary, J W; Ghiasi Shirazi, S M A; Hanson, G; Heilman, J; Jandir, P; Kennedy, E; Lacroix, F; Long, O R; Olmedo Negrete, M; Paneva, M I; Shrinivas, A; Si, W; Wei, H; Wimpenny, S; Yates, B R; Branson, J G; Cerati, G B; Cittolin, S; Derdzinski, M; Gerosa, R; Holzner, A; Klein, D; Krutelyov, V; Letts, J; Macneill, I; Olivito, D; Padhi, S; Pieri, M; Sani, M; Sharma, V; Simon, S; Tadel, M; Vartak, A; Wasserbaech, S; Welke, C; Wood, J; Würthwein, F; Yagil, A; Zevi Della Porta, G; Amin, N; Bhandari, R; Bradmiller-Feld, J; Campagnari, C; Dishaw, A; Dutta, V; Franco Sevilla, M; George, C; Golf, F; Gouskos, L; Gran, J; Heller, R; Incandela, J; Mullin, S D; Ovcharova, A; Qu, H; Richman, J; Stuart, D; Suarez, I; Yoo, J; Anderson, D; Bendavid, J; Bornheim, A; Bunn, J; Chen, Y; Duarte, J; Lawhorn, J M; Mott, A; Newman, H B; Pena, C; Spiropulu, M; Vlimant, J R; Xie, S; Zhu, R Y; Andrews, M B; Ferguson, T; Paulini, M; Russ, J; Sun, M; Vogel, H; Vorobiev, I; Weinberg, M; Cumalat, J P; Ford, W T; Jensen, F; Johnson, A; Krohn, M; Mulholland, T; Stenson, K; Wagner, S R; Alexander, J; Chaves, J; Chu, J; Dittmer, S; Mcdermott, K; Mirman, N; Nicolas Kaufman, G; Patterson, J R; Rinkevicius, A; Ryd, A; Skinnari, L; Soffi, L; Tan, S M; Tao, Z; Thom, J; Tucker, J; Wittich, P; Zientek, M; Winn, D; Abdullin, S; Albrow, M; Apollinari, G; Apresyan, A; Banerjee, S; Bauerdick, L A T; Beretvas, A; Berryhill, J; Bhat, P C; Bolla, G; Burkett, K; Butler, J N; Cheung, H W K; Chlebana, F; Cihangir, S; Cremonesi, M; Elvira, V D; Fisk, I; Freeman, J; Gottschalk, E; Gray, L; Green, D; Grünendahl, S; Gutsche, O; Hare, D; Harris, R M; Hasegawa, S; Hirschauer, J; Hu, Z; Jayatilaka, B; Jindariani, S; Johnson, M; Joshi, U; Klima, B; Kreis, B; Lammel, S; Linacre, J; Lincoln, D; Lipton, R; Liu, M; Liu, T; Lopes De Sá, R; Lykken, J; Maeshima, K; Magini, N; Marraffino, J M; Maruyama, S; Mason, D; McBride, P; Merkel, P; Mrenna, S; Nahn, S; O'Dell, V; Pedro, K; Prokofyev, O; Rakness, G; Ristori, L; Sexton-Kennedy, E; Soha, A; Spalding, W J; Spiegel, L; Stoynev, S; Strait, J; Strobbe, N; Taylor, L; Tkaczyk, S; Tran, N V; Uplegger, L; Vaandering, E W; Vernieri, C; Verzocchi, M; Vidal, R; Wang, M; Weber, H A; Whitbeck, A; Wu, Y; Acosta, D; Avery, P; Bortignon, P; Bourilkov, D; Brinkerhoff, A; Carnes, A; Carver, M; Curry, D; Das, S; Field, R D; Furic, I K; Konigsberg, J; Korytov, A; Low, J F; Ma, P; Matchev, K; Mei, H; Mitselmakher, G; Rank, D; Shchutska, L; Sperka, D; Thomas, L; Wang, J; Wang, S; Yelton, J; Linn, S; Markowitz, P; Martinez, G; Rodriguez, J L; Ackert, A; Adams, J R; Adams, T; Askew, A; Bein, S; Diamond, B; Hagopian, S; Hagopian, V; Johnson, K F; Prosper, H; Santra, A; Yohay, R; Baarmand, M M; Bhopatkar, V; Colafranceschi, S; Hohlmann, M; Noonan, D; Roy, T; Yumiceva, F; Adams, M R; Apanasevich, L; Berry, D; Betts, R R; Bucinskaite, I; Cavanaugh, R; Evdokimov, O; Gauthier, L; Gerber, C E; Hofman, D J; Jung, K; Kurt, P; O'Brien, C; Sandoval Gonzalez, I D; Turner, P; Varelas, N; Wang, H; Wu, Z; Zakaria, M; Zhang, J; Bilki, B; Clarida, W; Dilsiz, K; Durgut, S; Gandrajula, R P; Haytmyradov, M; Khristenko, V; Merlo, J-P; Mermerkaya, H; Mestvirishvili, A; Moeller, A; Nachtman, J; Ogul, H; Onel, Y; Ozok, F; Penzo, A; Snyder, C; Tiras, E; Wetzel, J; Yi, K; Anderson, I; Blumenfeld, B; Cocoros, A; Eminizer, N; Fehling, D; Feng, L; Gritsan, A V; Maksimovic, P; Martin, C; Osherson, M; Roskes, J; Sarica, U; Swartz, M; Xiao, M; Xin, Y; You, C; Al-Bataineh, A; Baringer, P; Bean, A; Boren, S; Bowen, J; Bruner, C; Castle, J; Forthomme, L; Kenny, R P; Khalil, S; Kropivnitskaya, A; Majumder, D; Mcbrayer, W; Murray, M; Sanders, S; Stringer, R; Tapia Takaki, J D; Wang, Q; Ivanov, A; Kaadze, K; Maravin, Y; Mohammadi, A; Saini, L K; Skhirtladze, N; Toda, S; Rebassoo, F; Wright, D; Anelli, C; Baden, A; Baron, O; Belloni, A; Calvert, B; Eno, S C; Ferraioli, C; Gomez, J A; Hadley, N J; Jabeen, S; Kellogg, R G; Kolberg, T; Kunkle, J; Lu, Y; Mignerey, A C; Ricci-Tam, F; Shin, Y H; Skuja, A; Tonjes, M B; Tonwar, S C; Abercrombie, D; Allen, B; Apyan, A; Azzolini, V; Barbieri, R; Baty, A; Bi, R; Bierwagen, K; Brandt, S; Busza, W; Cali, I A; D'Alfonso, M; Demiragli, Z; Di Matteo, L; Gomez Ceballos, G; Goncharov, M; Hsu, D; Iiyama, Y; Innocenti, G M; Klute, M; Kovalskyi, D; Krajczar, K; Lai, Y S; Lee, Y-J; Levin, A; Luckey, P D; Maier, B; Marini, A C; Mcginn, C; Mironov, C; Narayanan, S; Niu, X; Paus, C; Roland, C; Roland, G; Salfeld-Nebgen, J; Stephans, G S F; Tatar, K; Varma, M; Velicanu, D; Veverka, J; Wang, J; Wang, T W; Wyslouch, B; Yang, M; Zhukova, V; Benvenuti, A C; Chatterjee, R M; Evans, A; Finkel, A; Gude, A; Hansen, P; Kalafut, S; Kao, S C; Kubota, Y; Lesko, Z; Mans, J; Nourbakhsh, S; Ruckstuhl, N; Rusack, R; Tambe, N; Turkewitz, J; Acosta, J G; Oliveros, S; Avdeeva, E; Bartek, R; Bloom, K; Claes, D R; Dominguez, A; Fangmeier, C; Gonzalez Suarez, R; Kamalieddin, R; Kravchenko, I; Malta Rodrigues, A; Meier, F; Monroy, J; Siado, J E; Snow, G R; Stieger, B; Alyari, M; Dolen, J; George, J; Godshalk, A; Harrington, C; Iashvili, I; Kaisen, J; Kharchilava, A; Kumar, A; Parker, A; Rappoccio, S; Roozbahani, B; Alverson, G; Barberis, E; Hortiangtham, A; Massironi, A; Morse, D M; Nash, D; Orimoto, T; Teixeira De Lima, R; Trocino, D; Wang, R-J; Wood, D; Bhattacharya, S; Charaf, O; Hahn, K A; Kubik, A; Kumar, A; Mucia, N; Odell, N; Pollack, B; Schmitt, M H; Sung, K; Trovato, M; Velasco, M; Dev, N; Hildreth, M; Hurtado Anampa, K; Jessop, C; Karmgard, D J; Kellams, N; Lannon, K; Marinelli, N; Meng, F; Mueller, C; Musienko, Y; Planer, M; Reinsvold, A; Ruchti, R; Smith, G; Taroni, S; Wayne, M; Wolf, M; Woodard, A; Alimena, J; Antonelli, L; Bylsma, B; Durkin, L S; Flowers, S; Francis, B; Hart, A; Hill, C; Hughes, R; Ji, W; Liu, B; Luo, W; Puigh, D; Winer, B L; Wulsin, H W; Cooperstein, S; Driga, O; Elmer, P; Hardenbrook, J; Hebda, P; Lange, D; Luo, J; Marlow, D; Medvedeva, T; Mei, K; Mooney, M; Olsen, J; Palmer, C; Piroué, P; Stickland, D; Svyatkovskiy, A; Tully, C; Zuranski, A; Malik, S; Barker, A; Barnes, V E; Folgueras, S; Gutay, L; Jha, M K; Jones, M; Jung, A W; Khatiwada, A; Miller, D H; Neumeister, N; Schulte, J F; Shi, X; Sun, J; Wang, F; Xie, W; Parashar, N; Stupak, J; Adair, A; Akgun, B; Chen, Z; Ecklund, K M; Geurts, F J M; Guilbaud, M; Li, W; Michlin, B; Northup, M; Padley, B P; Redjimi, R; Roberts, J; Rorie, J; Tu, Z; Zabel, J; Betchart, B; Bodek, A; de Barbaro, P; Demina, R; Duh, Y T; Ferbel, T; Galanti, M; Garcia-Bellido, A; Han, J; Hindrichs, O; Khukhunaishvili, A; Lo, K H; Tan, P; Verzetti, M; Agapitos, A; Chou, J P; Contreras-Campana, E; Gershtein, Y; Gómez Espinosa, T A; Halkiadakis, E; Heindl, M; Hidas, D; Hughes, E; Kaplan, S; Kunnawalkam Elayavalli, R; Kyriacou, S; Lath, A; Nash, K; Saka, H; Salur, S; Schnetzer, S; Sheffield, D; Somalwar, S; Stone, R; Thomas, S; Thomassen, P; Walker, M; Delannoy, A G; Foerster, M; Heideman, J; Riley, G; Rose, K; Spanier, S; Thapa, K; Bouhali, O; Celik, A; Dalchenko, M; De Mattia, M; Delgado, A; Dildick, S; Eusebi, R; Gilmore, J; Huang, T; Juska, E; Kamon, T; Mueller, R; Pakhotin, Y; Patel, R; Perloff, A; Perniè, L; Rathjens, D; Rose, A; Safonov, A; Tatarinov, A; Ulmer, K A; Akchurin, N; Cowden, C; Damgov, J; De Guio, F; Dragoiu, C; Dudero, P R; Faulkner, J; Gurpinar, E; Kunori, S; Lamichhane, K; Lee, S W; Libeiro, T; Peltola, T; Undleeb, S; Volobouev, I; Wang, Z; Greene, S; Gurrola, A; Janjam, R; Johns, W; Maguire, C; Melo, A; Ni, H; Sheldon, P; Tuo, S; Velkovska, J; Xu, Q; Arenton, M W; Barria, P; Cox, B; Goodell, J; Hirosky, R; Ledovskoy, A; Li, H; Neu, C; Sinthuprasith, T; Sun, X; Wang, Y; Wolfe, E; Xia, F; Clarke, C; Harr, R; Karchin, P E; Sturdy, J; Belknap, D A; Buchanan, J; Caillol, C; Dasu, S; Dodd, L; Duric, S; Gomber, B; Grothe, M; Herndon, M; Hervé, A; Klabbers, P; Lanaro, A; Levine, A; Long, K; Loveless, R; Ojalvo, I; Perry, T; Pierro, G A; Polese, G; Ruggles, T; Savin, A; Smith, N; Smith, W H; Taylor, D; Woods, N

2017-04-21

The relative modification of the prompt ψ(2S) and J/ψ yields from pp to PbPb collisions, at the center-of-mass energy of 5.02 TeV per nucleon pair, is presented. The analysis is based on pp and PbPb data samples collected by the CMS experiment at the LHC in 2015, corresponding to integrated luminosities of 28.0  pb^{-1} and 464  μb^{-1}, respectively. The double ratio of measured yields of prompt charmonia reconstructed through their decays into muon pairs, (N_{ψ(2S)}/N_{J/ψ})_{PbPb}/(N_{ψ(2S)}/N_{J/ψ})_{pp}, is determined as a function of PbPb collision centrality and charmonium transverse momentum p_{T}, in two kinematic intervals: |y|<1.6 covering 6.5

Anticancer effect of PP31J isolated from Physalis pubescens L. in human cervical carcinoma cells

PubMed Central

Zeng, Wenjie; Wang, Qianqian; Chen, Lifeng; Huang, Lu; Zhao, Xiaofeng

2017-01-01

Extracts derived from Physalis pubescens L. may function as cancer therapies. The pharmacological effects of PP31J on human cervical carcinoma cells (HeLa cells) were investigated in this study. HeLa cells were treated with PP31J, and then cell proliferation, apoptosis, and cell cycle distribution were measured using a cell counting kit-8 (CCK-8) assay and flow cytometry. Protein expression levels of regulators of cell apoptosis and cell cycle were also examined using western blotting. Our data show that PP31J inhibited the growth of HeLa cells. Significant growth inhibition compared to the vehicle-treated group was observed using a concentration of 5 μM PP31J at 24, 48, and 72 h. PP31J also selectively arrested cell cycle progression in the G1 phase at 40 μM (P < 0.05) and in the G2/M phase at 20 μM (P < 0.01) and 40 μM (P < 0.001). Our results further demonstrate a significant increase in cell apoptosis (P < 0.001) following PP31J treatment (10, 20, and 40 μM). Immunoblotting data show that PP31J downregulated (P < 0.01) the expression of Bcl-xL and decreased (P < 0.05) the expression of Survivin and Cyclin D1 at 20 and 40 μM. This study shows the anti-tumor activity of PP31J in HeLa cells and that the effects of PP31J on cell cycle distribution and apoptosis induction were partially attributed to the regulation of Cyclin D1, Survivin, and Bcl-xL. PMID:28559997

Sensitivity and symptomology of marigold cultivars exposed to acute sulfur dioxide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Howe, T.K.; Woltz, S.S.

Thirty-nine cultivars of marigold (Tagetes spp.) were exposed to sulfur dioxide to determine their relative sensitivity. Flowering plants were fumigated at 1 ppM SO/sub 2/ for 4 hours or at 2 ppM SO/sub 2/ for 2 hours. The average foliar injury for all leaves on individual plants ranged from 42.3% for 'Crackerjack Mix' at 2 ppM SO/sub 2/ to 0.0% for 'Cupid Yellow' at 1 ppM SO/sub 2/. Foliar necrosis appeared as a gray to white marginal and/or interveinal scorch 1 day after exposure. There was a tendency for interveinal necrosis to be near the midvein. The extra-floral nectaries whichmore » line the leaf margins of marigold were scorched in 15 of the 39 cultivars. This injury may be of diagnostic value. Sepals were very sensitive to SO/sub 2/. Sepal injury appeared as a pinpoint scorch and as tip burn, and was apparent in some cultivars when no foliar injury occurred. 12 references, 1 figure, 1 table.« less

Induction of heme oxygenase-1 protects mouse liver from apoptotic ischemia/reperfusion injury.

PubMed

Ben-Ari, Z; Issan, Y; Katz, Y; Sultan, M; Safran, M; Michal, Laniado-Schwartzman; Nader, G Abraham; Kornowski, R; Grief, F; Pappo, O; Hochhauser, E

2013-05-01

Ischemia/reperfusion (I/R) injury is the main cause of primary graft dysfunction of liver allografts. Cobalt-protoporphyrin (CoPP)-dependent induction of heme oxygenase (HO)-1 has been shown to protect the liver from I/R injury. This study analyzes the apoptotic mechanisms of HO-1-mediated cytoprotection in mouse liver exposed to I/R injury. HO-1 induction was achieved by the administration of CoPP (1.5 mg/kg body weight i.p.). Mice were studied in in vivo model of hepatic segmental (70 %) ischemia for 60 min and reperfusion injury. Mice were randomly allocated to four main experimental groups (n = 10 each): (1) A control group undergoing sham operation. (2) Similar to group 1 but with the administration of CoPP 72 h before the operation. (3) Mice undergoing in vivo hepatic I/R. (4) Similar to group 3 but with the administration of CoPP 72 h before ischemia induction. When compared with the I/R mice group, in the I/R+CoPP mice group, the increased hepatic expression of HO-1 was associated with a significant reduction in liver enzyme levels, fewer apoptotic hepatocytes cells were identified by morphological criteria and by immunohistochemistry for caspase-3, there was a decreased mean number of proliferating cells (positively stained for Ki67), and a reduced hepatic expression of: C/EBP homologous protein (an index of endoplasmic reticulum stress), the NF-κB's regulated genes (CIAP2, MCP-1 and IL-6), and increased hepatic expression of IκBa (the inhibitory protein of NF-κB). HO-1 over-expression plays a pivotal role in reducing the hepatic apoptotic IR injury. HO-1 may serve as a potential target for therapeutic intervention in hepatic I/R injury during liver transplantation.

Alterations in GluR2 AMPA receptor phosphorylation at serine 880 following group I metabotropic glutamate receptor stimulation in the rat dorsal striatum.

PubMed

Ahn, Sung Min; Choe, Eun Sang

2010-04-01

Phosphorylation of ionotropic glutamate receptors in the brain plays a crucial role in the regulation of synaptic plasticity. In this study, we investigated the regulation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor phosphorylation by the stimulation of group I metabotropic glutamate receptors (mGluRs) in the dorsal striatum in vivo. The results showed that intrastriatal infusion of the group I mGluR agonist, (RS)-3,5-dihydroxyphenylglycine (DHPG, 250 nmol), enhanced the sensitivity of GluR2 subunit in its phosphorylation at serine 880 (S880) in the dorsal striatum. This enhancement of the sensitivity of GluR2-S880 phosphorylation was reduced by blocking group I mGluRs and N-methyl-D-aspartate (NMDA) receptors. Similar reduction of the enhancement was also induced by inhibiting phospholipase C (PLC), calcium/calmodulin-dependent protein kinase (CaMK), c-Jun N-terminal kinase (JNK), and protein kinase C (PKC). Inhibition of protein phosphatase (PP) 1/2A and calcineurin (PP2B) alone enhanced GluR2-S880 phosphorylation in the dorsal striatum, whereas inhibition of these phosphatases did not further enhance the S880 phosphorylation by DHPG stimulation. In addition, inhibition of PP1/2A or PP2B also enhanced the phosphorylation of CaMKII, JNK and PKC. These data suggest that the phosphorylation of AMPA receptor GluR2 subunit at S880 is subject to the upregulation by the stimulation of group I mGluRs. Interactions among glutamate receptors, protein kinases, and PPs participate in this upregulation. (c) 2009 Wiley-Liss, Inc.

Job Satisfaction, Organization Commitment and Retention in the NOAA (national Oceanic Atmospheric Administration) Corps

DTIC Science & Technology

1986-12-01

CONDUCT OF THE STUDY 21 B. THE QUESTIONNAIRE 21 C . THE SAMPLE 22 D. INSTRUMENTATION 23 E . ANALYSIS 23 F. PROCESSING THE RAW DATA 25 1. Crosstabulation 25...and Personality, 2d ed., pp. 35-58, Harper and Row, 1970. 2. Alderfer , C . P.. "An Empirical Test of a New Theory of Human Needs," Organizational...of Business Administration. 1965. 6. Hackman, R . J. and Lawier. E . E ., Journal of Applied Psvchoiogy. v. 55, no. 3. pp. 259-285. 1971. 7. Blood. M. R

Inhibition of serine/threonine phosphatase PP2A enhances cancer chemotherapy by blocking DNA damage induced defense mechanisms.

PubMed

Lu, Jie; Kovach, John S; Johnson, Francis; Chiang, Jeffrey; Hodes, Richard; Lonser, Russell; Zhuang, Zhengping

2009-07-14

A variety of mechanisms maintain the integrity of the genome in the face of cell stress. Cancer cell response to chemotherapeutic and radiation-induced DNA damage is mediated by multiple defense mechanisms including polo-like kinase 1 (Plk-1), protein kinase B (Akt-1), and/or p53 pathways leading to either apoptosis or cell cycle arrest. Subsequently, a subpopulation of arrested viable cancer cells may remain and recur despite aggressive and repetitive therapy. Here, we show that modulation (activation of Akt-1 and Plk-1 and repression of p53) of these pathways simultaneously results in paradoxical enhancement of the effectiveness of cytotoxic chemotherapy. We demonstrate that a small molecule inhibitor, LB-1.2, of protein phosphatase 2A (PP2A) activates Plk-1 and Akt-1 and decreases p53 abundance in tumor cells. Combined with temozolomide (TMZ; a DNA-methylating chemotherapeutic drug), LB-1.2 causes complete regression of glioblastoma multiforme (GBM) xenografts without recurrence in 50% of animals (up to 28 weeks) and complete inhibition of growth of neuroblastoma (NB) xenografts. Treatment with either drug alone results in only short-term inhibition/regression with all xenografts resuming rapid growth. Combined with another widely used anticancer drug, Doxorubicin (DOX, a DNA intercalating agent), LB-1.2 also causes marked GBM xenograft regression, whereas DOX alone only slows growth. Inhibition of PP2A by LB-1.2 blocks cell-cycle arrest and increases progression of cell cycle in the presence of TMZ or DOX. Pharmacologic inhibition of PP2A may be a general method for enhancing the effectiveness of cancer treatments that damage DNA or disrupt components of cell replication.

Short-term changes in quitting-related cognitions and behaviours after the implementation of plain packaging with larger health warnings: findings from a national cohort study with Australian adult smokers.

PubMed

Durkin, Sarah; Brennan, Emily; Coomber, Kerri; Zacher, Meghan; Scollo, Michelle; Wakefield, Melanie

2015-04-01

Plain packaging (PP) with larger graphic health warnings (GHWs) was implemented in Australia in late 2012. This study examined effects of these packaging changes on short-term changes in quitting-related cognitions and behaviours. We used a series of cohorts of Australian adult cigarette smokers originally sourced from a nationally representative cross-sectional tracking survey, followed up approximately 1 month after their baseline interview (n(weighted)=5441). Logistic regression analyses compared changes in seven quitting-related outcomes over this 1-month follow-up period for the cohorts surveyed before PP, over the period of transition to PP, and during the first year of PP, adjusting for baseline levels of the outcome and covariates. Compared to the referent group of smokers who completed their follow-up survey pre-PP, those who were followed-up in the early transition period showed significantly greater increases in rates of stopping themselves from smoking (OR=1.51, 95% CI (1.08 to 2.10)) and higher quit attempt rates (OR=1.43, 95% CI (1.00 to 2.03)), those followed-up in the late transition period showed greater increases in intentions to quit (OR=1.42, 95% CI (1.06 to 1.92)) and pack concealment (OR=1.55, 95% CI (1.05 to 2.31)), and those followed-up in the first year of PP showed higher levels of pack concealment (OR=1.65, 95% CI (1.01 to 2.72)), more premature stubbing out of cigarettes (OR=1.55, 95% CI (1.01 to 2.36)), and higher quit attempt rates (OR=1.52, 95% CI (1.01 to 2.30)). These findings provide some of the strongest evidence to date that implementation of PP with larger GHWs was associated with increased rates of quitting cognitions, microindicators of concern and quit attempts among adult cigarette smokers. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

URI Regulates KAP1 Phosphorylation and Transcriptional Repression via PP2A Phosphatase in Prostate Cancer Cells*

PubMed Central

Mita, Paolo; Savas, Jeffrey N.; Briggs, Erica M.; Ha, Susan; Gnanakkan, Veena; Yates, John R.; Robins, Diane M.; David, Gregory; Boeke, Jef D.; Garabedian, Michael J.; Logan, Susan K.

2016-01-01

URI (unconventional prefoldin RPB5 interactor protein) is an unconventional prefoldin, RNA polymerase II interactor that functions as a transcriptional repressor and is part of a larger nuclear protein complex. The components of this complex and the mechanism of transcriptional repression have not been characterized. Here we show that KAP1 (KRAB-associated protein 1) and the protein phosphatase PP2A interact with URI. Mechanistically, we show that KAP1 phosphorylation is decreased following recruitment of PP2A by URI. We functionally characterize the novel URI-KAP1-PP2A complex, demonstrating a role of URI in retrotransposon repression, a key function previously demonstrated for the KAP1-SETDB1 complex. Microarray analysis of annotated transposons revealed a selective increase in the transcription of LINE-1 and L1PA2 retroelements upon knockdown of URI. These data unveil a new nuclear function of URI and identify a novel post-transcriptional regulation of KAP1 protein that may have important implications in reactivation of transposable elements in prostate cancer cells. PMID:27780869

Protein Phosphatase-1 regulates Rift Valley fever virus replication.

PubMed

Baer, Alan; Shafagati, Nazly; Benedict, Ashwini; Ammosova, Tatiana; Ivanov, Andrey; Hakami, Ramin M; Terasaki, Kaori; Makino, Shinji; Nekhai, Sergei; Kehn-Hall, Kylene

2016-03-01

Rift Valley fever virus (RVFV), genus Phlebovirus family Bunyaviridae, is an arthropod-borne virus endemic throughout sub-Saharan Africa. Recent outbreaks have resulted in cyclic epidemics with an increasing geographic footprint, devastating both livestock and human populations. Despite being recognized as an emerging threat, relatively little is known about the virulence mechanisms and host interactions of RVFV. To date there are no FDA approved therapeutics or vaccines for RVF and there is an urgent need for their development. The Ser/Thr protein phosphatase 1 (PP1) has previously been shown to play a significant role in the replication of several viruses. Here we demonstrate for the first time that PP1 plays a prominent role in RVFV replication early on during the viral life cycle. Both siRNA knockdown of PP1α and a novel PP1-targeting small molecule compound 1E7-03, resulted in decreased viral titers across several cell lines. Deregulation of PP1 was found to inhibit viral RNA production, potentially through the disruption of viral RNA transcript/protein interactions, and indicates a potential link between PP1α and the viral L polymerase and nucleoprotein. These results indicate that PP1 activity is important for RVFV replication early on during the viral life cycle and may prove an attractive therapeutic target. Copyright © 2016 Elsevier B.V. All rights reserved.

Study of Z production in PbPb and pp collisions at $$ \\sqrt{s_{\\mathrm{NN}}}=2.76 $$ TeV in the dimuon and dielectron decay channels

DOE PAGES

Chatrchyan, Serguei

2015-03-04

We found that the production of Z bosons is studied in the dimuon and dielectron decay channels in PbPb and pp collisions at √s NN=2.76 TeV, using data collected by the CMS experiment at the LHC. The PbPb data sample corresponds to an integrated luminosity of about 166 μb -1, while the pp data sample collected in 2013 at the same nucleon-nucleon centre-of-mass energy has an integrated luminosity of 5.4 pb -1. The Z boson yield is measured as a function of rapidity, transverse momentum, and collision centrality. The ratio of PbPb to pp yields, scaled by the number ofmore » inelastic nucleon-nucleon collisions, is found to be 1.06 ± 0.05 (stat) ± 0.08 (syst) in the dimuon channel and 1.02 ± 0.08 (stat) ± 0.15 (syst) in the dielectron channel, for centrality-integrated Z boson production. Finally, this binary collision scaling is seen to hold in the entire kinematic region studied, as expected for a colourless probe that is unaffected by the hot and dense QCD medium produced in heavy ion collisions.« less

EphB4 Receptor Tyrosine Kinase in Prostate Cancer

DTIC Science & Technology

2011-09-01

San Diego, La Jolla, CA, USAAbbreviations: MAP kinase, mitogen-activated prote tidylinositol 4,5-bisphosphate; PI(3,4,5)P3, phosphatid PI3K...okadaic acid (MP Biomedicals, 150 μM stock in DMSO), LY294002, PD98059, rapamycin (see previous section), dasatinib (LC Laboratories; 50 μM stock in DMSO...the phosphatase inhibitor tautomycin, which preferentially inhibits PP1 over PP2A. The cells were stimulated and analyzed as in (D). (F) Okadaic acid

Rheological and mechanical properties of polypropylene prepared with multi-walled carbon nanotube masterbatch.

PubMed

Shim, Young-Sun; Park, Soo-Jin

2012-07-01

In this study, the effects of polypropylene-grafted maleic-anhydride-treated multi-walled carbon nanotubes (PP-MWNTs) on the viscoelastic behaviors and mechanical properties of a polypropylene-(PP)-based composite system were examined. The PP-MWNT/PP composites were prepared via melt mixing with a 3:1 ratio of PP-g-MA and acid-treated MWNTs at 220 degrees C. The surface characteristics of the PP-MWNTs were confirmed via Fourier transform infrared (FTIR) spectroscopy and transmission electron microscopy (TEM). The viscoelastic behavior and mechanical properties of the PP-MWNT/PP composites were confirmed using a rheometer and an ultimate testing machine (UTM). The storage and loss moduli increased with increasing PP-MWNT content. The critical intensity stress factor (K(IC)) of the PP-MWNT/PP composites at high filler loading was also higher than that of the MWNT/PP composites. In conclusion, the viscoelastic behavior and mechanical properties of MWNT/PP can be improved by grafting MWNTs to PP-g-MA.

Radiation-grafting of vinyl monomers separately onto polypropylene monofilament sutures

NASA Astrophysics Data System (ADS)

López-Saucedo, Felipe; Alvarez-Lorenzo, Carmen; Concheiro, Angel; Bucio, Emilio

2017-03-01

N-isopropylacrylamide (NIPAAm), 2-hydroxyethylmethacrylate (HEMA) and N-vinylimidazole (NVIm) were grafted separately onto polypropylene (PP) monofilament sutures. These grafted copolymers have properties with potential application in the synthesis of new medical devices. Co-60 gamma radiation was employed with dose rate of 9.2 kGyh-1 in synthesis of copolymers with different grafting percentages: PP-g-PNIPAAm from 11% to 175%, PP-g-PHEMA from 6% to 130%, and PP-g-PNVIm from 10% to 17%. Both NIPAAm and HEMA were grafted applying the pre-irradiation method under different reaction conditions: dose, temperature, monomer concentration and reaction time; NVIm was grafted by simultaneous method with doses from 20 up to 60 kGy. Grafted polymers were characterized by FTIR-ATR, TGA and DSC; and their swelling in water was recorded. Modified suture PP-g-PNIPAAm had thermo-responsive properties while PP-g-PNVIm exhibited pH-sensitive swelling. Overall, the implemented grafting strategies provided a hydrophilic surface layer that did not cause detrimental effects on mechanical properties and cytocompatibility of the sutures.

Tight regulation between cell survival and programmed cell death in GBM stem-like cells by EGFR/GSK3b/PP2A signaling.

PubMed

Gürsel, Demirkan B; Banu, Matei A; Berry, Nicholas; Marongiu, Roberta; Burkhardt, Jan-Karl; Kobylarz, Keith; Kaplitt, Michael G; Rafii, Shahin; Boockvar, John A

2015-01-01

Malignant gliomas represent one of the most aggressive forms of cancer, displaying high mortality rates and limited treatment options. Specific subpopulations of cells residing in the tumor niche with stem-like characteristics have been postulated to initiate and maintain neoplasticity while resisting conventional therapies. The study presented here aims to define the role of glycogen synthase kinase 3 beta (GSK3b) in patient-derived glioblastoma (GBM) stem-like cell (GSC) proliferation, apoptosis and invasion. To evaluate the potential role of GSK3b in GBM, protein profiles from 68 GBM patients and 20 normal brain samples were analyzed for EGFR-mediated PI3kinase/Akt and GSK3b signaling molecules including protein phosphatase 2A (PP2A). To better understand the function of GSK3b in GBM, GSCs were isolated from GBM patient samples. Blocking GSK3b phosphorylation at Serine 9 attenuated cell proliferation while concomitantly stimulating apoptosis through activation of Caspase-3 in patient-derived GSCs. Increasing GSK3b protein content resulted in the inhibition of cell proliferation, colony formation and stimulated programmed cell death. Depleting GSK3b in GSCs down regulated PP2A. Furthermore, knocking down PP2A or blocking its activity by okadaic acid inactivated GSK3b by increasing GSK3b phosphorylation at Serine 9. Our data suggests that GSK3b may function as a regulator of apoptosis and tumorigenesis in GSCs. Therapeutic approaches targeting GSK3b in glioblastoma stem-like cells may be a useful addition to our current therapeutic armamentarium.

Analysis of the in vitro and in vivo effects of photodynamic therapy on prostate cancer by using new photosensitizers, protoporphyrin IX-polyamine derivatives.

PubMed

Fidanzi-Dugas, Chloë; Liagre, Bertrand; Chemin, Guillaume; Perraud, Aurélie; Carrion, Claire; Couquet, Claude-Yves; Granet, Robert; Sol, Vincent; Léger, David Yannick

2017-07-01

Photodynamic therapy, using porphyrins as photosensitizers (PS), has been approved in treatment of several solid tumors. However, commonly used PS induce death but also resistance pathways in cancer cells and an alteration of surrounding normal tissues. Because polyamines (PA) are actively accumulated in cancer cells by the Polyamine Transport System (PTS), they may enable PS to specifically target cancer cells. Here, we investigated whether new protoporphyrin IX-polyamine derivatives were effective PS against prostate cancer and whether PA increased PDT specificity after 630nm irradiation. CHO and CHO-MG cells (differing in their PTS activity) were used to assess efficacy of polyamine vectorization. MTT assays were performed on human prostate non-malignant (RWPE-1) and malignant (PC-3, DU 145 and LNCaP) cell lines to test PS phototoxicity. ROS generation, DNA fragmentation and cell signalling were assessed by ELISA/EIA, western-blots and gel shift assays. Finally, PS effects were studied on tumor growth in nude mice. Our PS were more effective on cancer cells compared to non-malignant cells and more effective than PpIX alone. PpIX-PA generated ROS production involved in induction of apoptotic intrinsic pathways. Different pathways involved in apoptosis resistance were studied: PS inhibited Bcl-2, Akt, and NF-κB but activated p38/COX-2/PGE 2 pathways which were not implicated in apoptosis resistance in our model. In vivo experiments showed PpIX-PA efficacy was greater than results obtained with PpIX. All together, our results showed that PpIX-PA exerted its maximum effects without activating resistance pathways and appears to be a good candidate for prostate cancer PDT treatment. Copyright © 2017 Elsevier B.V. All rights reserved.